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Montgomery L, Larbi A. Monitoring Immune Responses to Vaccination: A Focus on Single-Cell Analysis and Associated Challenges. Vaccines (Basel) 2025; 13:420. [PMID: 40333304 PMCID: PMC12030821 DOI: 10.3390/vaccines13040420] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2025] [Revised: 04/13/2025] [Accepted: 04/15/2025] [Indexed: 05/09/2025] Open
Abstract
Monitoring the immune response to vaccination encompasses both significant challenges and promising opportunities for scientific advancement. The primary challenge lies in the inherent complexity and interindividual variability of immune responses, influenced by factors including age, genetic background, and prior immunological history. This variability necessitates the development of sophisticated, highly sensitive assays capable of accurately quantifying immune parameters such as antibody titers, T-cell responses, and cytokine profiles. Furthermore, the temporal dynamics of the immune response require comprehensive longitudinal studies to elucidate the durability and quality of vaccine-induced immunity. Challenges of this magnitude pave the way for immunological research advancements and diagnostic methodologies. Cutting-edge monitoring techniques, such as high-throughput sequencing and advanced flow cytometry, enable deeper insights into the mechanistic underpinnings of vaccine efficacy and contribute to the iterative design of more effective vaccines. Additionally, the integration of analytical tools holds the potential to predict immune responses and tailor personalized vaccination strategies. This will be addressed in this review to provide insight for enhancing public health outcomes and fortifying preparedness against future infectious disease threats.
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Affiliation(s)
- LaToya Montgomery
- Medical and Scientific Affairs, Beckman Coulter Life Sciences, Brea, CA 92821, USA;
| | - Anis Larbi
- Medical and Scientific Affairs, Beckman Coulter Life Sciences, Brea, CA 92821, USA;
- Department of Medicine, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, QC J1K 2R1, Canada
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Wagoner ZW, Yates TB, Hernandez-Davies JE, Sureshchandra S, Joloya EM, Jain A, de Assis R, Kastenschmidt JM, Sorn AM, Mitul MT, Tamburini I, Ahuja G, Zhong Q, Trask D, Seldin M, Davies DH, Wagar LE. Systems immunology analysis of human immune organoids identifies host-specific correlates of protection to different influenza vaccines. Cell Stem Cell 2025; 32:529-546.e6. [PMID: 39986275 PMCID: PMC11974613 DOI: 10.1016/j.stem.2025.01.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2024] [Revised: 11/27/2024] [Accepted: 01/27/2025] [Indexed: 02/24/2025]
Abstract
Vaccines are an essential tool to significantly reduce pathogen-related morbidity and mortality. However, our ability to rationally design vaccines and identify correlates of protection remains limited. Here, we employed an immune organoid approach to capture human adaptive immune response diversity to influenza vaccines and systematically identify host and antigen features linked to vaccine response variability. Our investigation identified established and unique immune signatures correlated with neutralizing antibody responses across seven different influenza vaccines and antigens. Unexpectedly, heightened ex vivo tissue frequencies of T helper (Th)1 cells emerged as both a predictor and a correlate of neutralizing antibody responses to inactivated influenza vaccines (IIVs). Secondary analysis of human public data confirmed that elevated Th1 signatures are associated with antibody responses following in vivo vaccination. These findings demonstrate the utility of human in vitro models for identifying in vivo correlates of protection and establish a role for Th1 functions in influenza vaccination.
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Affiliation(s)
- Zachary W Wagoner
- Department of Physiology & Biophysics, University of California, Irvine, Irvine, CA, USA; Institute for Immunology, University of California, Irvine, Irvine, CA, USA; Center for Virus Research, University of California, Irvine, Irvine, CA, USA; Vaccine R&D Center, University of California, Irvine, Irvine, CA, USA
| | - Timothy B Yates
- Department of Physiology & Biophysics, University of California, Irvine, Irvine, CA, USA; Institute for Immunology, University of California, Irvine, Irvine, CA, USA; Center for Virus Research, University of California, Irvine, Irvine, CA, USA; Vaccine R&D Center, University of California, Irvine, Irvine, CA, USA
| | - Jenny E Hernandez-Davies
- Department of Physiology & Biophysics, University of California, Irvine, Irvine, CA, USA; Institute for Immunology, University of California, Irvine, Irvine, CA, USA; Center for Virus Research, University of California, Irvine, Irvine, CA, USA; Vaccine R&D Center, University of California, Irvine, Irvine, CA, USA
| | - Suhas Sureshchandra
- Department of Physiology & Biophysics, University of California, Irvine, Irvine, CA, USA; Institute for Immunology, University of California, Irvine, Irvine, CA, USA; Center for Virus Research, University of California, Irvine, Irvine, CA, USA; Vaccine R&D Center, University of California, Irvine, Irvine, CA, USA
| | - Erika M Joloya
- Department of Physiology & Biophysics, University of California, Irvine, Irvine, CA, USA; Institute for Immunology, University of California, Irvine, Irvine, CA, USA; Center for Virus Research, University of California, Irvine, Irvine, CA, USA; Vaccine R&D Center, University of California, Irvine, Irvine, CA, USA
| | - Aarti Jain
- Department of Physiology & Biophysics, University of California, Irvine, Irvine, CA, USA; Institute for Immunology, University of California, Irvine, Irvine, CA, USA; Vaccine R&D Center, University of California, Irvine, Irvine, CA, USA
| | - Rafael de Assis
- Department of Physiology & Biophysics, University of California, Irvine, Irvine, CA, USA; Institute for Immunology, University of California, Irvine, Irvine, CA, USA; Vaccine R&D Center, University of California, Irvine, Irvine, CA, USA
| | - Jenna M Kastenschmidt
- Department of Physiology & Biophysics, University of California, Irvine, Irvine, CA, USA; Institute for Immunology, University of California, Irvine, Irvine, CA, USA; Center for Virus Research, University of California, Irvine, Irvine, CA, USA; Vaccine R&D Center, University of California, Irvine, Irvine, CA, USA
| | - Andrew M Sorn
- Department of Physiology & Biophysics, University of California, Irvine, Irvine, CA, USA; Institute for Immunology, University of California, Irvine, Irvine, CA, USA; Center for Virus Research, University of California, Irvine, Irvine, CA, USA; Vaccine R&D Center, University of California, Irvine, Irvine, CA, USA
| | - Mahina Tabassum Mitul
- Department of Physiology & Biophysics, University of California, Irvine, Irvine, CA, USA; Institute for Immunology, University of California, Irvine, Irvine, CA, USA; Center for Virus Research, University of California, Irvine, Irvine, CA, USA; Vaccine R&D Center, University of California, Irvine, Irvine, CA, USA
| | - Ian Tamburini
- Department of Biological Chemistry, University of California, Irvine, Irvine, CA, USA; Center for Epigenetics and Metabolism, University of California, Irvine, Irvine, CA, USA
| | - Gurpreet Ahuja
- Department of Pediatric Otolaryngology, Children's Hospital of Orange County, Orange, CA, USA; Department of Otolaryngology-Head and Neck Surgery, University of California, Irvine, Orange, CA, USA
| | - Qiu Zhong
- Department of Pediatric Otolaryngology, Children's Hospital of Orange County, Orange, CA, USA; Department of Otolaryngology-Head and Neck Surgery, University of California, Irvine, Orange, CA, USA
| | - Douglas Trask
- Department of Otolaryngology-Head and Neck Surgery, University of California, Irvine, Orange, CA, USA
| | - Marcus Seldin
- Department of Biological Chemistry, University of California, Irvine, Irvine, CA, USA; Center for Epigenetics and Metabolism, University of California, Irvine, Irvine, CA, USA
| | - D Huw Davies
- Department of Physiology & Biophysics, University of California, Irvine, Irvine, CA, USA; Institute for Immunology, University of California, Irvine, Irvine, CA, USA; Center for Virus Research, University of California, Irvine, Irvine, CA, USA; Vaccine R&D Center, University of California, Irvine, Irvine, CA, USA
| | - Lisa E Wagar
- Department of Physiology & Biophysics, University of California, Irvine, Irvine, CA, USA; Institute for Immunology, University of California, Irvine, Irvine, CA, USA; Center for Virus Research, University of California, Irvine, Irvine, CA, USA; Vaccine R&D Center, University of California, Irvine, Irvine, CA, USA.
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3
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Jung Y, Hwang J, Cho H, Yoon JH, Lee JH, Song J, Kim D, Ahn M, Hong BH, Kweon DH. Graphene quantum dots as potential broad-spectrum antiviral agents. NANOSCALE ADVANCES 2025; 7:2032-2038. [PMID: 39974343 PMCID: PMC11833456 DOI: 10.1039/d4na00879k] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/25/2024] [Accepted: 01/24/2025] [Indexed: 02/21/2025]
Abstract
As pandemic viruses have become a threat to people, various treatments have been developed, including vaccines, neutralizing antibodies, and inhibitors. However, some mutations in the target envelope protein limit the efficiency of these treatments. Therefore, the development of broad-spectrum antiviral agents targeting mutation-free viral membranes is of considerable importance. Herein, we propose graphene quantum dots (GQDs) as broad-spectrum antiviral agents, wherein the amphiphilic properties of GQDs destroy the viral membranes, regardless of the type of viruses, including SARS-CoV-2 and influenza virus. We observed that GQDs suppress both viral infection and replication and demonstrated their low cytotoxicity in a cell line and a mouse model, revealing the potential of GQDs as a universal first-line treatment for various viral diseases.
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Affiliation(s)
- Younghun Jung
- Department of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan University Suwon 16419 Republic of Korea
| | - Jaehyeon Hwang
- Department of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan University Suwon 16419 Republic of Korea
| | - Hyeonwoo Cho
- Department of Chemistry, Seoul National University Seoul 08826 Republic of Korea
- Graphene Research Center & Graphene Square Chemical Inc., Advanced Institute of Convergence Technology Suwon 16229 Republic of Korea
| | - Jeong Hyeon Yoon
- Department of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan University Suwon 16419 Republic of Korea
| | - Jong-Hwan Lee
- Department of Chemistry, Seoul National University Seoul 08826 Republic of Korea
| | - Jaekwang Song
- Department of Chemistry, Seoul National University Seoul 08826 Republic of Korea
| | - Donghoon Kim
- Department of Pharmacology, Peripheral Neuropathy Research Center (PNRC), Dong-A University College of Medicine Busan 49201 Republic of Korea
| | - Minchul Ahn
- Department of Chemistry, Seoul National University Seoul 08826 Republic of Korea
- Graphene Research Center & Graphene Square Chemical Inc., Advanced Institute of Convergence Technology Suwon 16229 Republic of Korea
| | - Byung Hee Hong
- Department of Chemistry, Seoul National University Seoul 08826 Republic of Korea
- Graphene Research Center & Graphene Square Chemical Inc., Advanced Institute of Convergence Technology Suwon 16229 Republic of Korea
| | - Dae-Hyuk Kweon
- Department of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan University Suwon 16419 Republic of Korea
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Kifle DW, Balkhi MY, Ono Y, Davis J, Doi N, Arya A, Kim J, Kalyanasundaram A, Nandy S, Rakotozandrindrainy N, Staker B, Craig J, Rakotozandrindrainy R, Tadesse BT, Marks F, Jackson L, Carter D, Gray SA, Siddiqui AA. A functional enzymatic assay as potential readout for a clinical trial of a schistosomiasis vaccine. NPJ Vaccines 2025; 10:48. [PMID: 40082479 PMCID: PMC11906860 DOI: 10.1038/s41541-024-01044-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Accepted: 11/29/2024] [Indexed: 03/16/2025] Open
Abstract
An estimated 200 million people are currently infected with schistosomiasis and an additional 800 million reside in high transmission-risk areas in 78 endemic countries. In this report we describe a functional enzymatic assay based on the core calpain antigen (Sm-p80) of the schistosomiasis vaccine, SchistoShield®. A 44 kDa soluble variant of the core Sm-p80 antigen (B7), was assessed for its enzymatic activity using a fluorescent synthetic substrate. Inhibition of the B7 enzymatic activity by Sm-p80-specific antibodies obtained from pre-clinical trials in rodents, non-human primates as well as from participants of the human clinical trials was measured. The B7 enzyme activity followed a Michaelis-Menten-like kinetic behavior. Statistically significant inhibition of the B7 activity was observed by Sm-p80-specific antibodies produced by immunized mice, non-human primates and humans. This quantitative serological assay could be of value in assessing the effectiveness of the SchistoShield® vaccine in human trials in Africa.
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Affiliation(s)
- Desalegn W Kifle
- Department of Immunology & Molecular Microbiology and Center for Tropical Medicine and Infectious Diseases, Texas Tech University Health Sciences Center, Lubbock, TX, USA
| | - Mumtaz Y Balkhi
- Department of Immunology & Molecular Microbiology and Center for Tropical Medicine and Infectious Diseases, Texas Tech University Health Sciences Center, Lubbock, TX, USA
| | - Yasuko Ono
- Calpain Project, Department of Basic Medical Sciences, Tokyo Metropolitan Institute of Medical Science (TMiMS), 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo, 1568506, Japan
| | | | - Naoko Doi
- Calpain Project, Department of Basic Medical Sciences, Tokyo Metropolitan Institute of Medical Science (TMiMS), 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo, 1568506, Japan
| | - Aryandra Arya
- Department of Immunology & Molecular Microbiology and Center for Tropical Medicine and Infectious Diseases, Texas Tech University Health Sciences Center, Lubbock, TX, USA
| | - Jiho Kim
- PAI Life Sciences Inc, Seattle, WA, USA
| | - Aravindan Kalyanasundaram
- Department of Immunology & Molecular Microbiology and Center for Tropical Medicine and Infectious Diseases, Texas Tech University Health Sciences Center, Lubbock, TX, USA
| | - Sourav Nandy
- Department of Immunology & Molecular Microbiology and Center for Tropical Medicine and Infectious Diseases, Texas Tech University Health Sciences Center, Lubbock, TX, USA
| | | | - Bart Staker
- Seattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, WA, USA
| | - Justin Craig
- Seattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, WA, USA
| | | | - Birkneh T Tadesse
- Madagascar Institute for Vaccine Research (MIVR), University of Antananarivo, Antananarivo, Madagascar
- International Vaccine Institute, SNU Research Park, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, Korea, Republic of Korea
- Department of Global Public Health, Karolinska Institutet, Stockholm, Sweden
- Center for Innovative Drug Development and Therapeutic Trials for Africa, College of Health Sciences, Addis Ababa University, Addis Ababa, P.O. Box 9086, Ethiopia
| | - Florian Marks
- Madagascar Institute for Vaccine Research (MIVR), University of Antananarivo, Antananarivo, Madagascar
- International Vaccine Institute, SNU Research Park, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, Korea, Republic of Korea
- Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, CB2 0AW, UK
- Heidelberg Institute of Global Health, University of Heidelberg, Im Neuenheimer Feld 130/3, 69120, Heidelberg, Germany
| | - Lisa Jackson
- Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA
| | | | | | - Afzal A Siddiqui
- Department of Immunology & Molecular Microbiology and Center for Tropical Medicine and Infectious Diseases, Texas Tech University Health Sciences Center, Lubbock, TX, USA.
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5
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Xiao W, Jiang W, Chen Z, Huang Y, Mao J, Zheng W, Hu Y, Shi J. Advance in peptide-based drug development: delivery platforms, therapeutics and vaccines. Signal Transduct Target Ther 2025; 10:74. [PMID: 40038239 PMCID: PMC11880366 DOI: 10.1038/s41392-024-02107-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Revised: 11/01/2024] [Accepted: 12/13/2024] [Indexed: 03/06/2025] Open
Abstract
The successful approval of peptide-based drugs can be attributed to a collaborative effort across multiple disciplines. The integration of novel drug design and synthesis techniques, display library technology, delivery systems, bioengineering advancements, and artificial intelligence have significantly expedited the development of groundbreaking peptide-based drugs, effectively addressing the obstacles associated with their character, such as the rapid clearance and degradation, necessitating subcutaneous injection leading to increasing patient discomfort, and ultimately advancing translational research efforts. Peptides are presently employed in the management and diagnosis of a diverse array of medical conditions, such as diabetes mellitus, weight loss, oncology, and rare diseases, and are additionally garnering interest in facilitating targeted drug delivery platforms and the advancement of peptide-based vaccines. This paper provides an overview of the present market and clinical trial progress of peptide-based therapeutics, delivery platforms, and vaccines. It examines the key areas of research in peptide-based drug development through a literature analysis and emphasizes the structural modification principles of peptide-based drugs, as well as the recent advancements in screening, design, and delivery technologies. The accelerated advancement in the development of novel peptide-based therapeutics, including peptide-drug complexes, new peptide-based vaccines, and innovative peptide-based diagnostic reagents, has the potential to promote the era of precise customization of disease therapeutic schedule.
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Affiliation(s)
- Wenjing Xiao
- Department of Pharmacy, The General Hospital of Western Theater Command, Chengdu, 610083, China
| | - Wenjie Jiang
- Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, China
| | - Zheng Chen
- School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610031, China
| | - Yu Huang
- School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610031, China
| | - Junyi Mao
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China
| | - Wei Zheng
- Department of Integrative Medicine, Xinqiao Hospital, Army Medical University, Chongqing, 400037, China
| | - Yonghe Hu
- School of Medicine, Southwest Jiaotong University, Chengdu, 610031, China
| | - Jianyou Shi
- Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, China.
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Saadh MJ, Muhammad FA, Albadr RJ, Sanghvi G, Jyothi SR, Kundlas M, Joshi KK, Gulyamov S, Taher WM, Alwan M, Jawad MJ, Al-Nuaimi AMA. From protein to immunology: comprehensive insights into Marburg virus vaccines, mechanism, and application. Arch Microbiol 2025; 207:74. [PMID: 40025302 DOI: 10.1007/s00203-025-04277-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2025] [Revised: 02/05/2025] [Accepted: 02/12/2025] [Indexed: 03/04/2025]
Abstract
The Marburg virus (MARV), a member of the Filoviridae family, is a highly lethal pathogen that causes Marburg virus disease (MVD), a severe hemorrhagic fever with high fatality rates.Despite recurrent outbreaks, no licensed vaccine is currently available. This review explores MARV's genomic architecture, structural proteins, and recent advancements in vaccine development. It highlights the crucial role of MARV's seven monocistronic genes in viral replication and pathogenesis, with a focus on structural proteins such as nucleoprotein (NP), glycoprotein (GP), and viral proteins VP35, VP40, and VP24. These proteins are essential for viral entry, immune evasion, and replication. The review further examines various vaccine platforms, including multi-epitope vaccines, DNA-based vaccines, viral vector vaccines, virus-like particles (VLPs), and mRNA vaccines. Cutting-edge immunoinformatics approaches are discussed for identifying conserved epitopes critical for broad-spectrum protection. The immunological responses induced by these vaccine candidates, particularly their efficacy in preclinical trials, are analyzed, showcasing promising results in generating both humoral and cellular immunity. Moreover, the review addresses challenges and future directions in MARV vaccine development, emphasizing the need for enhanced immunogenicity, safety, and global accessibility. The integration of omics technologies (genomics, transcriptomics, proteomics) with immunoinformatics is presented as a transformative approach for next-generation vaccine design. Innovative platforms such as mRNA and VLP-based vaccines offer rapid and effective development opportunities. In this study, underscores the urgent need for a licensed MARV vaccine to prevent future outbreaks and strengthen global preparedness. By synthesizing the latest research and technological advancements, it provides a strategic roadmap for developing safe, effective, and broadly protective vaccines. The fight against MARV is a global priority, requiring coordinated efforts from researchers, policymakers, and public health organizations.
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Affiliation(s)
- Mohamed J Saadh
- Faculty of Pharmacy, Middle East University, Amman, 11831, Jordan
| | | | | | - Gaurav Sanghvi
- Marwadi University Research Center, Department of Microbiology, Faculty of Science, Marwadi University, Rajkot, Gujarat, 360003, India
| | - S Renuka Jyothi
- Department of Biotechnology and Genetics, School of Sciences, JAIN (Deemed to Be University), Bangalore, Karnataka, India
| | - Mayank Kundlas
- Centre for Research Impact and Outcome, Chitkara University Institute of Engineering and Technology, Chitkara University, Rajpura, Punjab, 140401, India
| | - Kamal Kant Joshi
- Department of Allied Science, Graphic Era Hill University, Dehradun, Uttarakhand, 248002, India
- Graphic Era Deemed to Be University, Dehradun, Uttarakhand, India
| | - Surat Gulyamov
- Department of Dentistry and Pediatric Dentistry, Tashkent Pediatric Medical Institute, Bogishamol Street 223, 100140, Tashkent, Uzbekistan
| | - Waam Mohammed Taher
- College of Nursing, National University of Science and Technology, Dhi Qar, Iraq
| | - Mariem Alwan
- Pharmacy College, Al-Farahidi University, Baghdad, Iraq
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Adugna T, Niu Q, Guan G, Du J, Yang J, Tian Z, Yin H. Advancements in nanoparticle-based vaccine development against Japanese encephalitis virus: a systematic review. Front Immunol 2024; 15:1505612. [PMID: 39759527 PMCID: PMC11695416 DOI: 10.3389/fimmu.2024.1505612] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2024] [Accepted: 11/25/2024] [Indexed: 01/07/2025] Open
Abstract
Vaccination remains the sole effective strategy for combating Japanese encephalitis (JE). Both inactivated and live attenuated vaccines exhibit robust immunogenicity. However, the production of these conventional vaccine modalities necessitates extensive cultivation of the pathogen, incurring substantial costs and presenting significant biosafety risks. Moreover, the administration of live pathogens poses potential hazards for individuals or animals with compromised immune systems or other health vulnerabilities. Subsequently, ongoing research endeavors are focused on the development of next-generation JE vaccines utilizing nanoparticle (NP) platforms. This systematic review seeks to aggregate the research findings pertaining to NP-based vaccine development against JE. A thorough literature search was conducted across established English-language databases for research articles on JE NP vaccine development published between 2000 and 2023. A total of twenty-eight published studies were selected for detailed analysis in this review. Of these, 16 studies (57.14%) concentrated on virus-like particles (VLPs) employing various structural proteins. Other approaches, including sub-viral particles (SVPs), biopolymers, and both synthetic and inorganic NP platforms, were utilized to a lesser extent. The results of these investigations indicated that, despite variations in the usage of adjuvants, dosages, NP types, antigenic proteins, and animal models employed across different studies, the candidate NP vaccines developed were capable of eliciting enhanced humoral and cellular adaptive immune responses, providing effective protection (70-100%) for immunized mice against lethal challenges posed by virulent Japanese encephalitis virus (JEV). In conclusion, prospective next-generation JE vaccines for humans and animals may emerge from these candidate formulations following further evaluation in subsequent vaccine development phases.
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Affiliation(s)
- Takele Adugna
- State Key Laboratory for Animal Disease Control and Prevention, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China
- Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, State Key Laboratory of Veterinary Etiological Biology Project, Yangzhou, China
- College of Veterinary Medicine and Animal Sciences, University of Gondar, Gondar, Ethiopia
| | - Qingli Niu
- State Key Laboratory for Animal Disease Control and Prevention, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China
- Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, State Key Laboratory of Veterinary Etiological Biology Project, Yangzhou, China
| | - Guiquan Guan
- State Key Laboratory for Animal Disease Control and Prevention, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China
- Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, State Key Laboratory of Veterinary Etiological Biology Project, Yangzhou, China
| | - Junzheng Du
- State Key Laboratory for Animal Disease Control and Prevention, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China
- Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, State Key Laboratory of Veterinary Etiological Biology Project, Yangzhou, China
| | - Jifei Yang
- State Key Laboratory for Animal Disease Control and Prevention, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China
- Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, State Key Laboratory of Veterinary Etiological Biology Project, Yangzhou, China
| | - Zhancheng Tian
- State Key Laboratory for Animal Disease Control and Prevention, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China
- Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, State Key Laboratory of Veterinary Etiological Biology Project, Yangzhou, China
| | - Hong Yin
- State Key Laboratory for Animal Disease Control and Prevention, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China
- Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, State Key Laboratory of Veterinary Etiological Biology Project, Yangzhou, China
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8
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Guo J, Zheng B, Chen T, Guo S, Liu M, Dong S. Prioritizing vaccine introduction to China's National Immunization Program: a multi-criteria decision analysis. BMC Public Health 2024; 24:3458. [PMID: 39695502 DOI: 10.1186/s12889-024-21013-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Accepted: 12/06/2024] [Indexed: 12/20/2024] Open
Abstract
BACKGROUND To prioritize the introducing of new vaccines into China's National Immunization Program (NIP) among 10 candidate vaccines across four classes. METHODS We developed a vaccine value framework using Multi-Criteria Decision Analysis (MCDA) to simulate the introduction of new vaccines into NIP, covering 21 criteria encompassing six dimensions: safety, effectiveness, economy, innovation, accessibility, and appropriateness. Two decision scenarios were considered: Scenario One prioritized the four classes of vaccines, while Scenario Two identified specific vaccines within each class. RESULTS In the vaccine value framework, safety received the highest weight, while innovation received the lowest. The Human Papillomavirus (HPV) vaccine was identified as a top priority for inclusion in NIP, followed by Pneumococcal Conjugate Vaccine (PCV), Haemophilus Influenzae Type B (HIB), and Rotavirus (RV) vaccines. The specific types are domestic bivalent HPV vaccine, imported 13-valent PCV vaccine, domestic HIB vaccine, and domestic RV vaccine. The results of the one-way and probabilistic sensitivity analysis demonstrated robustness. CONCLUSIONS This study provides a transparent, comprehensive, and quantifiable vaccine value framework to aid decision-making for introducing new vaccines into China's NIP. According to the MCDA results, HPV should be considered the top vaccine candidate for the NIP.
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Affiliation(s)
- Jianming Guo
- Department of Pharmacy, Sanming Second Hospital, Sanming, Fujian Province, China
- Department of Pharmacy, Fujian Medical University Union Hospital, Fujian, 350000, People's Republic of China
- National Institute of Hospital Administration, National Health Commission, Beijing, 100080, China
| | - Bin Zheng
- Department of Pharmacy, Fujian Medical University Union Hospital, Fujian, 350000, People's Republic of China
| | - Tingting Chen
- Department of Pharmacy, Fujian Medical University Union Hospital, Fujian, 350000, People's Republic of China
| | - Shuyan Guo
- National Institute of Hospital Administration, National Health Commission, Beijing, 100080, China
| | - Maobai Liu
- Department of Pharmacy, Fujian Medical University Union Hospital, Fujian, 350000, People's Republic of China.
| | - Siping Dong
- National Institute of Hospital Administration, National Health Commission, Beijing, 100080, China.
- School of Political Science and Public Administration, Wuhan University, Wuhan, China.
- Health Research Institute, Fujian Medical University, Fujian, China.
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9
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Semancik CS, Whitworth HS, Price MA, Yun H, Postler TS, Zaric M, Kilianski A, Cooper CL, Kuteesa M, Talasila S, Malkevich N, Gupta SB, Francis SC. Seroprevalence of Antibodies to Filoviruses with Outbreak Potential in Sub-Saharan Africa: A Systematic Review to Inform Vaccine Development and Deployment. Vaccines (Basel) 2024; 12:1394. [PMID: 39772055 PMCID: PMC11726543 DOI: 10.3390/vaccines12121394] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2024] [Revised: 11/27/2024] [Accepted: 12/09/2024] [Indexed: 01/16/2025] Open
Abstract
Background/Objectives: Orthoebolaviruses and orthomarburgviruses are filoviruses that can cause viral hemorrhagic fever and significant morbidity and mortality in humans. The evaluation and deployment of vaccines to prevent and control Ebola and Marburg outbreaks must be informed by an understanding of the transmission and natural history of the causative infections, but little is known about the burden of asymptomatic infection or undiagnosed disease. This systematic review of the published literature examined the seroprevalence of antibodies to orthoebolaviruses and orthomarburgviruses in sub-Saharan Africa. Methods: The review protocol was registered on PROSPERO (ID: CRD42023415358) and previously published. Eighty-seven articles describing 85 studies were included, of which seventy-six measured antibodies to orthoebolaviruses and forty-one measured antibodies to orthomarburgviruses. Results: The results highlight three central findings that may have implications for vaccine development and deployment. First, substantial antibody seropositivity to Ebola virus (EBOV) and Sudan virus (SUDV) was observed in populations from outbreak-affected areas (≤33% seroprevalence among general populations; ≤41% seroprevalence among healthcare workers and close contacts of disease cases). Second, antibody seropositivity to EBOV, SUDV, and Marburg virus (MARV) was observed among populations from areas without reported outbreaks, with seroprevalence ranging from <1 to 21%. Third, in Central and East Africa, MARV antibody seroprevalence was substantially lower than EBOV or SUDV antibody seroprevalence, even in outbreak-affected areas and in populations at a moderate or high risk of infection (with MARV seroprevalence mostly ranging from 0 to 3%). Conclusions: Whilst gaps remain in our understanding of the significance of antibody seropositivity in some settings and contexts, these findings may be important in considering target indications for novel filovirus vaccines, in defining study designs and strategies for demonstrating vaccine efficacy or effectiveness, and in planning and evaluating vaccine deployment strategies to prevent and control outbreaks.
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Affiliation(s)
- Christopher S. Semancik
- IAVI, 125 Broad St, New York, NY 10004, USA
- Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, MA 02111, USA
| | | | - Matt A. Price
- IAVI, 125 Broad St, New York, NY 10004, USA
- Department of Epidemiology and Biostatistics, University of California at San Francisco, San Francisco, CA 94143, USA
| | - Heejin Yun
- IAVI, 125 Broad St, New York, NY 10004, USA
| | - Thomas S. Postler
- Vaccine Design and Development Laboratory, IAVI, Brooklyn, NY 11220, USA
| | | | | | | | | | | | | | | | - Suzanna C. Francis
- IAVI, 125 Broad St, New York, NY 10004, USA
- Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK
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10
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Cagigi A, Tinnirello R, Iannolo G, Douradinha B. Orthoflavivirus zikaense (Zika) vaccines: What are we waiting for? Int J Antimicrob Agents 2024; 64:107367. [PMID: 39490448 DOI: 10.1016/j.ijantimicag.2024.107367] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Revised: 10/08/2024] [Accepted: 10/20/2024] [Indexed: 11/05/2024]
Affiliation(s)
- Alberto Cagigi
- International Vaccine Institute (IVI) Europe Regional Office, Solna, Sweden
| | | | | | - Bruno Douradinha
- Vaccine Technology Subgroup, Emerging Pathogens Group, Pandemic Sciences Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
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11
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He L, Zhu Z, Qi C. β-Glucan-A promising immunocyte-targeting drug delivery vehicle: Superiority, applications and future prospects. Carbohydr Polym 2024; 339:122252. [PMID: 38823919 DOI: 10.1016/j.carbpol.2024.122252] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Revised: 05/07/2024] [Accepted: 05/08/2024] [Indexed: 06/03/2024]
Abstract
Drug delivery technologies that could convert promising therapeutics into successful therapies have been under broad research for many years. Recently, β-glucans, natural-occurring polysaccharides extracted from many organism species such as yeast, fungi and bacteria, have attracted increasing attention to serve as drug delivery carriers. With their unique structure and innate immunocompetence, β-glucans are considered as promising carriers for targeting delivery especially when applied in the vaccine construction and oral administration of therapeutic agents. In this review, we focus on three types of β-glucans applied in the drug delivery system including yeast β-glucan, Schizophyllan and curdlan, highlighting the benefits of β-glucan based delivery system. We summarize how β-glucans as delivery vehicles have aided various therapeutics ranging from macromolecules including proteins, peptides and nucleic acids to small molecular drugs to reach desired cells or organs in terms of loading strategies. We also outline the challenges and future directions for developing the next generation of β-glucan based delivery systems.
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Affiliation(s)
- Liuyang He
- The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou Medical Center, Changzhou 213003, China
| | - Zhichao Zhu
- The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou Medical Center, Changzhou 213003, China
| | - Chunjian Qi
- The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou Medical Center, Changzhou 213003, China.
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12
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Graciaa DS, Walsh SR, Rouphael N. Human Immunodeficiency Virus Vaccine: Promise and Challenges. Infect Dis Clin North Am 2024; 38:475-485. [PMID: 38876903 PMCID: PMC11305931 DOI: 10.1016/j.idc.2024.04.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/16/2024]
Abstract
Development of a safe and effective human immunodeficiency virus (HIV) vaccine is a persistent challenge despite decades of research. Previous strategies utilizing protein subunit and viral vector vaccines were safe but not protective. Current strategies seek to induce broadly neutralizing antibodies, with multiple early phase trials in progress seeking to achieve this through sequential vaccination, mRNA, or updated viral-vectored vaccines. A safe and effective vaccine is critical to ending the HIV epidemic.
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Affiliation(s)
- Daniel S Graciaa
- Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA; Hope Clinic of Emory Vaccine Center, 500 Irvin Court, Suite 200, Decatur, GA 30030, USA.
| | - Stephen R Walsh
- Division of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA
| | - Nadine Rouphael
- Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA; Hope Clinic of Emory Vaccine Center, 500 Irvin Court, Suite 200, Decatur, GA 30030, USA
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13
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Henríquez R, Muñoz-Barroso I. Viral vector- and virus-like particle-based vaccines against infectious diseases: A minireview. Heliyon 2024; 10:e34927. [PMID: 39144987 PMCID: PMC11320483 DOI: 10.1016/j.heliyon.2024.e34927] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2024] [Revised: 06/28/2024] [Accepted: 07/18/2024] [Indexed: 08/16/2024] Open
Abstract
To overcome the limitations of conventional vaccines, new platforms for vaccine design have emerged such as those based on viral vectors and virus-like particles (VLPs). Viral vector vaccines are highly efficient and the onset of protection is quick. Many recombinant vaccine candidates for humans are based on viruses belonging to different families such as Adenoviridae, Retroviridae, Paramyxoviridae, Rhabdoviridae, and Parvoviridae. Also, the first viral vector vaccine licensed for human vaccination was the Japanese encephalitis virus vaccine. Since then, several viral vectors have been approved for vaccination against the viruses of Lassa fever, Ebola, hepatitis B, hepatitis E, SARS-CoV-2, and malaria. VLPs are nanoparticles that mimic viral particles formed from the self-assembly of structural proteins and VLP-based vaccines against hepatitis B and E viruses, human papillomavirus, and malaria have been commercialized. As evidenced by the accelerated production of vaccines against COVID-19, these new approaches are important tools for vaccinology and for generating rapid responses against pathogens and emerging pandemic threats.
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Affiliation(s)
- Ruth Henríquez
- Departamento de Bioquímica y Biología Molecular, Universidad de Salamanca, Edificio Departamental Lab.106. Plaza Doctores de la Reina S/n, 37007, Salamanca, Spain
| | - Isabel Muñoz-Barroso
- Departamento de Bioquímica y Biología Molecular, Universidad de Salamanca, Edificio Departamental Lab.106. Plaza Doctores de la Reina S/n, 37007, Salamanca, Spain
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14
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Lin WZ, Hung CM, Lin IH, Sun YJ, Liao ZX, Wu CC, Hou SY. Enhancing antibody detection sensitivity in lateral flow immunoassays using endospores of Bacillus subtilis as signal amplifiers. Talanta 2024; 276:126215. [PMID: 38723474 DOI: 10.1016/j.talanta.2024.126215] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Revised: 03/28/2024] [Accepted: 05/05/2024] [Indexed: 06/14/2024]
Abstract
Antibody detection is the critical first step for tracking the spread of many diseases including COVID-19. Lateral flow immunoassay (LFIA) is the most commonly used method for rapid antibody detection because it is easy-to-use and inexpensive. However, LFIA has limited sensitivity when gold nanoparticles (AuNPs) are used as the signals. In this study, the endospores of Bacillus subtilis were used in combination with AuNP in a LFIA to detect antibodies. The endospores serve as a signal amplifier. The detection limit was about 10-8 M for anti-beta galactosidase antibody detection whereas the detection limit of conventional LFIA is about 10-6 M. Furthermore, the proposed methods have no additional user steps compared with the traditional LFIA. This method, therefore, improved the sensitivity 100-fold without compromising any advantages of LFIA. We believe that the proposed method will be useful for detection of antibodies against HIV, Zika virus, SARS-CoV-2, and so on.
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Affiliation(s)
- Wen-Zhi Lin
- Department and Graduate Institute of Microbiology and Immunology, National Defense Medical Center, Taipei, 11490, Taiwan; Institute of Preventive Medicine, National Defense Medical Center, New Taipei City, 23742, Taiwan; Department of Biology and Anatomy, National Defense Medical Center, Taipei, 11490, Taiwan.
| | - Chin-Mao Hung
- Institute of Preventive Medicine, National Defense Medical Center, New Taipei City, 23742, Taiwan; Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, 11490, Taiwan.
| | - I-Hsien Lin
- Graduate Institute of Chemical Engineering, Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, Taipei, 10608, Taiwan.
| | - Yi-Jia Sun
- Graduate Institute of Biochemical and Biomedical Engineering, Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, Taipei, 10608, Taiwan.
| | - Zheng-Xiu Liao
- Graduate Institute of Chemical Engineering, Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, Taipei, 10608, Taiwan.
| | - Chia-Chun Wu
- Institute of Preventive Medicine, National Defense Medical Center, New Taipei City, 23742, Taiwan; Department of Orthopaedic Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, 11490, Taiwan.
| | - Shao-Yi Hou
- Graduate Institute of Biochemical and Biomedical Engineering, Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, Taipei, 10608, Taiwan.
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15
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Truex N, Mohapatra S, Melo M, Rodriguez J, Li N, Abraham W, Sementa D, Touti F, Keskin DB, Wu CJ, Irvine DJ, Gómez-Bombarelli R, Pentelute BL. Design of Cytotoxic T Cell Epitopes by Machine Learning of Human Degrons. ACS CENTRAL SCIENCE 2024; 10:793-802. [PMID: 38680558 PMCID: PMC11046456 DOI: 10.1021/acscentsci.3c01544] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Revised: 02/13/2024] [Accepted: 02/16/2024] [Indexed: 05/01/2024]
Abstract
Antigen processing is critical for therapeutic vaccines to generate epitopes for priming cytotoxic T cell responses against cancer and pathogens, but insufficient processing often limits the quantity of epitopes released. We address this challenge using machine learning to ascribe a proteasomal degradation score to epitope sequences. Epitopes with varying scores were translocated into cells using nontoxic anthrax proteins. Epitopes with a low score show pronounced immunogenicity due to antigen processing, but epitopes with a high score show limited immunogenicity. This work sheds light on the sequence-activity relationships between proteasomal degradation and epitope immunogenicity. We anticipate that future efforts to incorporate proteasomal degradation signals into vaccine designs will lead to enhanced cytotoxic T cell priming by these vaccines in clinical settings.
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Affiliation(s)
- Nicholas
L. Truex
- Department
of Chemistry, Massachusetts Institute of
Technology, Cambridge, Massachusetts 02139, United States
- Department
of Chemistry and Biochemistry, University
of South Carolina, Columbia, South Carolina 29208, United States
| | - Somesh Mohapatra
- Department
of Materials Science and Engineering, Massachusetts
Institute of Technology, Cambridge, Massachusetts 02139, United States
- Machine
Intelligence and Manufacturing Operations Group, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States
| | - Mariane Melo
- The
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, United States
- Ragon Institute
of Massachusetts General Hospital, Massachusetts
Institute of Technology, and Harvard University, Cambridge, Massachusetts 02139, United States
| | - Jacob Rodriguez
- Department
of Chemistry, Massachusetts Institute of
Technology, Cambridge, Massachusetts 02139, United States
| | - Na Li
- The
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, United States
| | - Wuhbet Abraham
- The
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, United States
| | - Deborah Sementa
- Department
of Chemistry, Massachusetts Institute of
Technology, Cambridge, Massachusetts 02139, United States
| | - Faycal Touti
- Department
of Chemistry, Massachusetts Institute of
Technology, Cambridge, Massachusetts 02139, United States
| | - Derin B. Keskin
- Department
of Medical Oncology, Dana-Farber Cancer
Institute, Boston, Massachusetts 02215, United States
- Harvard
Medical School, Boston, Massachusetts 02115, United States
- Broad
Institute of MIT and Harvard, Cambridge, Massachusetts 02142, United States
- Translational
Immunogenomics Laboratory (TIGL), Dana-Farber
Cancer Institute, Boston, Massachusetts 02215, United States
- Department
of Computer Science, Metropolitan College, Boston University, Boston, Massachusetts 02215, United States
- Section
for Bioinformatics, Department of Health Technology, Technical University of Denmark, Lyngby DK-2800, Denmark
| | - Catherine J. Wu
- Department
of Medical Oncology, Dana-Farber Cancer
Institute, Boston, Massachusetts 02215, United States
- Harvard
Medical School, Boston, Massachusetts 02115, United States
- Broad
Institute of MIT and Harvard, Cambridge, Massachusetts 02142, United States
- Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts 02115, United States
| | - Darrell J. Irvine
- Department
of Materials Science and Engineering, Massachusetts
Institute of Technology, Cambridge, Massachusetts 02139, United States
- The
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, United States
- Ragon Institute
of Massachusetts General Hospital, Massachusetts
Institute of Technology, and Harvard University, Cambridge, Massachusetts 02139, United States
- Department
of Biological Engineering, Massachusetts
Institute of Technology, Cambridge, Massachusetts 02139, United States
- Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, United States
| | - Rafael Gómez-Bombarelli
- Department
of Materials Science and Engineering, Massachusetts
Institute of Technology, Cambridge, Massachusetts 02139, United States
| | - Bradley L. Pentelute
- Department
of Chemistry, Massachusetts Institute of
Technology, Cambridge, Massachusetts 02139, United States
- The
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, United States
- Broad
Institute of MIT and Harvard, Cambridge, Massachusetts 02142, United States
- Center
for Environmental Health Sciences, Massachusetts
Institute of Technology, Cambridge, Massachusetts 02139, United States
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16
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Hou Y, Chen M, Bian Y, Hu Y, Chuan J, Zhong L, Zhu Y, Tong R. Insights into vaccines for elderly individuals: from the impacts of immunosenescence to delivery strategies. NPJ Vaccines 2024; 9:77. [PMID: 38600250 PMCID: PMC11006855 DOI: 10.1038/s41541-024-00874-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Accepted: 03/28/2024] [Indexed: 04/12/2024] Open
Abstract
Immunosenescence increases the risk and severity of diseases in elderly individuals and leads to impaired vaccine-induced immunity. With aging of the global population and the emerging risk of epidemics, developing adjuvants and vaccines for elderly individuals to improve their immune protection is pivotal for healthy aging worldwide. Deepening our understanding of the role of immunosenescence in vaccine efficacy could accelerate research focused on optimizing vaccine delivery for elderly individuals. In this review, we analyzed the characteristics of immunosenescence at the cellular and molecular levels. Strategies to improve vaccination potency in elderly individuals are summarized, including increasing the antigen dose, preparing multivalent antigen vaccines, adding appropriate adjuvants, inhibiting chronic inflammation, and inhibiting immunosenescence. We hope that this review can provide a review of new findings with regards to the impacts of immunosenescence on vaccine-mediated protection and inspire the development of individualized vaccines for elderly individuals.
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Affiliation(s)
- Yingying Hou
- Department of Pharmacy, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, China
- Personalized Drug Therapy Key Laboratory of Sichuan Province, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, China
| | - Min Chen
- Department of Pharmacy, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, China
- Personalized Drug Therapy Key Laboratory of Sichuan Province, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, China
| | - Yuan Bian
- Department of Pharmacy, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, China
- Personalized Drug Therapy Key Laboratory of Sichuan Province, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, China
| | - Yuan Hu
- Department of Pharmacy, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, China
- Personalized Drug Therapy Key Laboratory of Sichuan Province, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, China
| | - Junlan Chuan
- Department of Pharmacy, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, China
- Personalized Drug Therapy Key Laboratory of Sichuan Province, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, China
| | - Lei Zhong
- Department of Pharmacy, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, China.
- Personalized Drug Therapy Key Laboratory of Sichuan Province, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, China.
| | - Yuxuan Zhu
- Department of Pharmacy, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, China.
- Personalized Drug Therapy Key Laboratory of Sichuan Province, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, China.
| | - Rongsheng Tong
- Department of Pharmacy, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, China.
- Personalized Drug Therapy Key Laboratory of Sichuan Province, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, China.
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17
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Arega AM, Dhal AK, Pattanaik KP, Nayak S, Mahapatra RK. An Immunoinformatics-Based Study of Mycobacterium tuberculosis Region of Difference-2 Uncharacterized Protein (Rv1987) as a Potential Subunit Vaccine Candidate for Preliminary Ex Vivo Analysis. Appl Biochem Biotechnol 2024; 196:2367-2395. [PMID: 37498378 DOI: 10.1007/s12010-023-04658-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/04/2023] [Indexed: 07/28/2023]
Abstract
Mycobacterium tuberculosis (Mtb) is the pathogen that causes tuberculosis and develops resistance to many of the existing drugs. The sole licensed TB vaccine, BCG, is unable to provide a comprehensive defense. So, it is crucial to maintain the immunological response to eliminate tuberculosis. Our previous in silico study reported five uncharacterized proteins as potential vaccine antigens. In this article, we considered the uncharacterized Mtb H37Rv regions of difference (RD-2) Rv1987 protein as a promising vaccine candidate. The vaccine quality of the protein was analyzed using reverse vaccinology and immunoinformatics-based quality-checking parameters followed by an ex vivo preliminary investigation. In silico analysis of Rv1987 protein predicted it as surface localized, secretory, single helix, antigenic, non-allergenic, and non-homologous to the host protein. Immunoinformatics analysis of Rv1987 by CD4 + and CD8 + T-cells via MHC-I and MHC-II binding affinity and presence of B-cell epitope predicted its immunogenicity. The docked complex analysis of the 3D model structure of the protein with immune cell receptor TLR-4 revealed the protein's capability for potential interaction. Furthermore, the target protein-encoded gene Rv1987 was cloned, over-expressed, purified, and analyzed by mass spectrometry (MS) to report the target peptides. The qRT-PCR gene expression analysis shows that it is capable of activating macrophages and significantly increasing the production of a number of key cytokines (TNF-α, IL-1β, and IL-10). Our in-silico analysis and ex vivo preliminary investigations revealed the immunogenic potential of the target protein. These findings suggest that the Rv1987 be undertaken as a potent subunit vaccine antigen and that further animal model immuno-modulation studies would boost the novel TB vaccine discovery and/or BCG vaccine supplement pipeline.
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Affiliation(s)
- Aregitu Mekuriaw Arega
- School of Biotechnology, KIIT Deemed to Be University, Bhubaneswar, Odisha, India
- National Veterinary Institute, Debre Zeit, Ethiopia
| | - Ajit Kumar Dhal
- School of Biotechnology, KIIT Deemed to Be University, Bhubaneswar, Odisha, India
| | | | - Sasmita Nayak
- School of Biotechnology, KIIT Deemed to Be University, Bhubaneswar, Odisha, India
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18
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ElSherif M, Halperin SA. Benefits of Combining Molecular Biology and Controlled Human Infection Model Methodologies in Advancing Vaccine Development. J Mol Biol 2023; 435:168322. [PMID: 37866477 DOI: 10.1016/j.jmb.2023.168322] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Revised: 10/13/2023] [Accepted: 10/17/2023] [Indexed: 10/24/2023]
Abstract
Infectious diseases continue to account for a significant portion of global deaths despite the use of vaccines for several centuries. Immunization programs around the world are a testament to the great success of multiple vaccines, yet there are still diseases without vaccines and others that require safer more effective ones. Addressing uncontrolled and emerging disease threats is restrained by the limitations and bottlenecks encountered with traditional vaccine development paradigms. Recent advances in modern molecular biology technologies have enhanced the interrogation of host pathogen interaction and deciphered complex pathways, thereby uncovering the myriad interplay of biological events that generate immune protection against foreign agents. Consequent to insights into the immune system, modern biology has been instrumental in the development and production of next generation 21st century vaccines. As these biological tools, commonly and collectively referred to as 'omics, became readily available, there has been a renewed consideration of Controlled Human Infection Models (CHIMs). Successful and reproducible CHIMs can complement modern molecular biology for the study of infectious diseases and development of effective vaccines in a regulated process that mitigates risk, cost, and time, with capacity to discern immune correlates of protection.
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Affiliation(s)
- May ElSherif
- Canadian Center for Vaccinology, IWK Health, Nova Scotia Health, and Dalhousie University, Halifax, Nova Scotia, Canada.
| | - Scott A Halperin
- Canadian Center for Vaccinology, IWK Health, Nova Scotia Health, and Dalhousie University, Halifax, Nova Scotia, Canada.
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19
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Zheng Z, Wu X, Wang Y, Yang X, Chen H, Shen Y, Yang Y, Xia Q. Attenuating RNA Viruses with Expanded Genetic Codes to Evoke Adjustable Immune Response in PylRS-tRNACUAPyl Transgenic Mice. Vaccines (Basel) 2023; 11:1606. [PMID: 37897007 PMCID: PMC10610612 DOI: 10.3390/vaccines11101606] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2023] [Revised: 09/03/2023] [Accepted: 09/24/2023] [Indexed: 10/29/2023] Open
Abstract
Ribonucleic acid (RNA) viruses pose heavy burdens on public-health systems. Synthetic biology holds great potential for artificially controlling their replication, a strategy that could be used to attenuate infectious viruses but is still in the exploratory stage. Herein, we used the genetic-code expansion technique to convert Enterovirus 71 (EV71), a prototypical RNA virus, into a controllable EV71 strain carrying the unnatural amino acid (UAA) Nε-2-azidoethyloxycarbonyl-L-lysine (NAEK), which we termed an EV71-NAEK virus. After NAEK supplementation, EV71-NAEK could recapitulate an authentic NAEK time- and dose-dependent infection in vitro, which could serve as a novel method to manipulate virulent viruses in conventional laboratories. We further validated the prophylactic effect of EV71-NAEK in two mouse models. In susceptible parent mice, vaccination with EV71-NAEK elicited a strong immune response and protected their neonatal offspring from lethal challenges similar to that of commercial vaccines. Meanwhile, in transgenic mice harboring a PylRS-tRNACUAPyl pair, substantial elements of genetic-code expansion technology, EV71-NAEK evoked an adjustable neutralizing-antibody response in a strictly external NAEK dose-dependent manner. These findings suggested that EV71-NAEK could be the basis of a feasible immunization program for populations with different levels of immunity. Moreover, we expanded the strategy to generate controllable coxsackieviruses for conceptual verification. In combination, these results could underlie a competent strategy for attenuating viruses and priming the immune system via artificial control, which might be a promising direction for the development of amenable vaccine candidates and be broadly applied to other RNA viruses.
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Affiliation(s)
| | | | | | | | | | | | | | - Qing Xia
- State Key Laboratory of Natural and Biomimetic Drugs, Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China; (Z.Z.); (X.W.); (Y.W.); (X.Y.); (H.C.); (Y.S.); (Y.Y.)
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20
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Truex NL, Mohapatra S, Melo M, Rodriguez J, Li N, Abraham W, Sementa D, Touti F, Keskin DB, Wu CJ, Irvine DJ, Gómez-Bombarelli R, Pentelute BL. Design of Cytotoxic T Cell Epitopes by Machine Learning of Human Degrons. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.08.22.554289. [PMID: 37662211 PMCID: PMC10473641 DOI: 10.1101/2023.08.22.554289] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/05/2023]
Abstract
Antigen processing is critical for producing epitope peptides that are presented by HLA molecules for T cell recognition. Therapeutic vaccines aim to harness these epitopes for priming cytotoxic T cell responses against cancer and pathogens, but insufficient processing often reduces vaccine efficacy through limiting the quantity of epitopes released. Here, we set out to improve antigen processing by harnessing protein degradation signals called degrons from the ubiquitin-proteasome system. We used machine learning to generate a computational model that ascribes a proteasomal degradation score between 0 and 100. Epitope peptides with varying degron activities were synthesized and translocated into cells using nontoxic anthrax proteins: protective antigen (PA) and the N-terminus of lethal factor (LFN). Immunogenicity studies revealed epitope sequences with a low score (<25) show pronounced T-cell activation but epitope sequences with a higher score (>75) provide limited activation. This work sheds light on the sequence-activity relationships between proteasomal degradation and epitope immunogenicity, through conserving the epitope region but varying the flanking sequence. We anticipate that future efforts to incorporate proteasomal degradation signals into vaccine designs will lead to enhanced cytotoxic T cell priming by vaccine therapeutics in clinical settings.
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Affiliation(s)
- Nicholas L. Truex
- Department of Chemistry, Massachusetts Institute of Technology; 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA
- Department of Chemistry and Biochemistry, University of South Carolina; 631 Sumter St., Columbia, South Carolina, 29208, USA
| | - Somesh Mohapatra
- Department of Materials Science and Engineering, Massachusetts Institute of Technology; 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA
- Machine Intelligence and Manufacturing Operations Group, Massachusetts Institute of Technology; 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA
| | - Mariane Melo
- The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology; 500 Main Street, Cambridge, Massachusetts 02142, USA
- Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology; 400 Technology Square, Cambridge, Massachusetts 02139, USA
| | - Jacob Rodriguez
- Department of Chemistry, Massachusetts Institute of Technology; 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA
| | - Na Li
- The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology; 500 Main Street, Cambridge, Massachusetts 02142, USA
| | - Wuhbet Abraham
- The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology; 500 Main Street, Cambridge, Massachusetts 02142, USA
| | - Deborah Sementa
- Department of Chemistry, Massachusetts Institute of Technology; 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA
| | - Faycal Touti
- Department of Chemistry, Massachusetts Institute of Technology; 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA
| | - Derin B. Keskin
- Department of Medical Oncology, Dana-Farber Cancer Institute; Boston, Massachusetts, 02215, USA
- Harvard Medical School; Boston, Massachusetts, 02115, USA
- Broad Institute of MIT and Harvard; Cambridge, Massachusetts, USA
- Translational Immunogenomics Laboratory (TIGL), Dana-Farber Cancer Institute; Boston, Massachusetts, 02215, USA
- Department of Computer Science, Metropolitan College, Boston University; Boston, Massachusetts, USA
- Section for Bioinformatics, Department of Health Technology, Technical University of Denmark; Lyngby, DK
| | - Catherine J. Wu
- Department of Medical Oncology, Dana-Farber Cancer Institute; Boston, Massachusetts, 02215, USA
- Harvard Medical School; Boston, Massachusetts, 02115, USA
- Broad Institute of MIT and Harvard; Cambridge, Massachusetts, USA
- Department of Medicine, Brigham and Women’s Hospital; Boston, MA 02215, USA
| | - Darrell J. Irvine
- Department of Materials Science and Engineering, Massachusetts Institute of Technology; 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA
- The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology; 500 Main Street, Cambridge, Massachusetts 02142, USA
- Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology; 400 Technology Square, Cambridge, Massachusetts 02139, USA
- Department of Biological Engineering, Massachusetts Institute of Technology; 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA
- Howard Hughes Medical Institute; 4000 Jones Bridge Rd, Chevy Chase, Maryland 20815, USA
| | - Rafael Gómez-Bombarelli
- Department of Materials Science and Engineering, Massachusetts Institute of Technology; 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA
| | - Bradley L. Pentelute
- Department of Chemistry, Massachusetts Institute of Technology; 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA
- The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology; 500 Main Street, Cambridge, Massachusetts 02142, USA
- Broad Institute of MIT and Harvard; Cambridge, Massachusetts, USA
- Center for Environmental Health Sciences, Massachusetts Institute of Technology; 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA
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21
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He X, Wang J, Tang Y, Chiang ST, Han T, Chen Q, Qian C, Shen X, Li R, Ai X. Recent Advances of Emerging Spleen-Targeting Nanovaccines for Immunotherapy. Adv Healthc Mater 2023; 12:e2300351. [PMID: 37289567 DOI: 10.1002/adhm.202300351] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Revised: 05/19/2023] [Indexed: 06/10/2023]
Abstract
Vaccines provide a powerful tool to modulate the immune system for human disease prevention and treatment. Classical vaccines mainly initiate immune responses in the lymph nodes (LNs) after subcutaneous injection. However, some vaccines suffer from inefficient delivery of antigens to LNs, undesired inflammation, and slow immune induction when encountering the rapid proliferation of tumors. Alternatively, the spleen, as the largest secondary lymphoid organ with a high density of antigen-presenting cells (APCs) and lymphocytes, acts as an emerging target organ for vaccinations in the body. Upon intravenous administration, the rationally designed spleen-targeting nanovaccines can be internalized by the APCs in the spleen to induce selective antigen presentation to T and B cells in their specific sub-regions, thereby rapidly boosting durable cellular and humoral immunity. Herein, the recent advances of spleen-targeting nanovaccines for immunotherapy based on the anatomical architectures and functional zones of the spleen, as well as their limitations and perspectives for clinical applications are systematically summarized. The aim is to emphasize the design of innovative nanovaccines for enhanced immunotherapy of intractable diseases in the future.
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Affiliation(s)
- Xuanyi He
- Department of Bioengineering, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, No. 800 Dongchuan Road, Shanghai, 200240, China
| | - Jing Wang
- Department of Bioengineering, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, No. 800 Dongchuan Road, Shanghai, 200240, China
| | - Yuqing Tang
- Department of Bioengineering, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, No. 800 Dongchuan Road, Shanghai, 200240, China
| | - Seok Theng Chiang
- Department of Bioengineering, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, No. 800 Dongchuan Road, Shanghai, 200240, China
| | - Tianzhen Han
- Department of Bioengineering, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, No. 800 Dongchuan Road, Shanghai, 200240, China
| | - Qi Chen
- Department of Bioengineering, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, No. 800 Dongchuan Road, Shanghai, 200240, China
| | - Chunxi Qian
- Department of Bioengineering, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, No. 800 Dongchuan Road, Shanghai, 200240, China
| | - Xiaoshuai Shen
- Department of Bioengineering, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, No. 800 Dongchuan Road, Shanghai, 200240, China
| | - Rongxiu Li
- Department of Bioengineering, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, No. 800 Dongchuan Road, Shanghai, 200240, China
| | - Xiangzhao Ai
- Department of Bioengineering, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, No. 800 Dongchuan Road, Shanghai, 200240, China
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22
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Hou Y, Chen M, Bian Y, Zheng X, Tong R, Sun X. Advanced subunit vaccine delivery technologies: From vaccine cascade obstacles to design strategies. Acta Pharm Sin B 2023; 13:3321-3338. [PMID: 37655334 PMCID: PMC10465871 DOI: 10.1016/j.apsb.2023.01.006] [Citation(s) in RCA: 30] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2022] [Revised: 11/23/2022] [Accepted: 12/03/2022] [Indexed: 01/12/2023] Open
Abstract
Designing and manufacturing safe and effective vaccines is a crucial challenge for human health worldwide. Research on adjuvant-based subunit vaccines is increasingly being explored to meet clinical needs. Nevertheless, the adaptive immune responses of subunit vaccines are still unfavorable, which may partially be attributed to the immune cascade obstacles and unsatisfactory vaccine design. An extended understanding of the crosstalk between vaccine delivery strategies and immunological mechanisms could provide scientific insight to optimize antigen delivery and improve vaccination efficacy. In this review, we summarized the advanced subunit vaccine delivery technologies from the perspective of vaccine cascade obstacles after administration. The engineered subunit vaccines with lymph node and specific cell targeting ability, antigen cross-presentation, T cell activation properties, and tailorable antigen release patterns may achieve effective immune protection with high precision, efficiency, and stability. We hope this review can provide rational design principles and inspire the exploitation of future subunit vaccines.
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Affiliation(s)
- Yingying Hou
- Department of Pharmacy, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China
- Personalized Drug Therapy Key Laboratory of Sichuan Province, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China
| | - Min Chen
- Department of Pharmacy, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China
- Personalized Drug Therapy Key Laboratory of Sichuan Province, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China
| | - Yuan Bian
- Department of Pharmacy, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China
- Personalized Drug Therapy Key Laboratory of Sichuan Province, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China
| | - Xi Zheng
- Department of Pharmacy, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China
- Personalized Drug Therapy Key Laboratory of Sichuan Province, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China
| | - Rongsheng Tong
- Department of Pharmacy, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China
- Personalized Drug Therapy Key Laboratory of Sichuan Province, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China
| | - Xun Sun
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China
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23
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Cao F, Peng S, An Y, Xu K, Zheng T, Dai L, Ogino K, Ngai T, Xia Y, Ma G. Inside-out assembly of viral antigens for the enhanced vaccination. Signal Transduct Target Ther 2023; 8:189. [PMID: 37221173 DOI: 10.1038/s41392-023-01414-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Revised: 01/13/2023] [Accepted: 03/08/2023] [Indexed: 05/25/2023] Open
Abstract
Current attempts in vaccine delivery systems concentrate on replicating the natural dissemination of live pathogens, but neglect that pathogens evolve to evade the immune system rather than to provoke it. In the case of enveloped RNA viruses, it is the natural dissemination of nucleocapsid protein (NP, core antigen) and surface antigen that delays NP exposure to immune surveillance. Here, we report a multi-layered aluminum hydroxide-stabilized emulsion (MASE) to dictate the delivery sequence of the antigens. In this manner, the receptor-binding domain (RBD, surface antigen) of the spike protein was trapped inside the nanocavity, while NP was absorbed on the outside of the droplets, enabling the burst release of NP before RBD. Compared with the natural packaging strategy, the inside-out strategy induced potent type I interferon-mediated innate immune responses and triggered an immune-potentiated environment in advance, which subsequently boosted CD40+ DC activations and the engagement of the lymph nodes. In both H1N1 influenza and SARS-CoV-2 vaccines, rMASE significantly increased antigen-specific antibody secretion, memory T cell engagement, and Th1-biased immune response, which diminished viral loads after lethal challenge. By simply reversing the delivery sequence of the surface antigen and core antigen, the inside-out strategy may offer major implications for enhanced vaccinations against the enveloped RNA virus.
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Affiliation(s)
- Fengqiang Cao
- State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, PR China
- Graduate School of Bio-Applications and Systems Engineering, Tokyo University of Agriculture and Technology, 2-24-16 Nakacho, Koganei, Tokyo, 184-8588, Japan
- Institute of Global Innovation Research, Tokyo University of Agriculture and Technology, 2-24-16 Nakacho, Koganei-shi, Tokyo, 184-8588, Japan
| | - Sha Peng
- State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, PR China
- Graduate School of Bio-Applications and Systems Engineering, Tokyo University of Agriculture and Technology, 2-24-16 Nakacho, Koganei, Tokyo, 184-8588, Japan
- Institute of Global Innovation Research, Tokyo University of Agriculture and Technology, 2-24-16 Nakacho, Koganei-shi, Tokyo, 184-8588, Japan
| | - Yaling An
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, PR China
- Savaid Medical School, University of Chinese Academy of Sciences, Beijing, PR China
| | - Kun Xu
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, PR China
- Key Laboratory of Tropical Translational Medicine of Ministry of Education, School of Tropical Medicine and Laboratory Medicine, The First Affiliated Hospital, Hainan Medical University, Hainan, 571199, PR China
| | - Tianyi Zheng
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, PR China
- Zhejiang University School of Medicine, Hangzhou, 310058, PR China
| | - Lianpan Dai
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, PR China
| | - Kenji Ogino
- Graduate School of Bio-Applications and Systems Engineering, Tokyo University of Agriculture and Technology, 2-24-16 Nakacho, Koganei, Tokyo, 184-8588, Japan.
- Institute of Global Innovation Research, Tokyo University of Agriculture and Technology, 2-24-16 Nakacho, Koganei-shi, Tokyo, 184-8588, Japan.
| | - To Ngai
- Department of Chemistry, The Chinese University of Hong Kong, Shatin, N. T., Hong Kong, 999077, PR China
| | - Yufei Xia
- State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, PR China.
- University of Chinese Academy of Sciences, Beijing, 100049, PR China.
- Innovation Academy for Green Manufacture Chinese Academy of Sciences, Beijing, 100190, PR China.
| | - Guanghui Ma
- State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, PR China.
- Institute of Global Innovation Research, Tokyo University of Agriculture and Technology, 2-24-16 Nakacho, Koganei-shi, Tokyo, 184-8588, Japan.
- University of Chinese Academy of Sciences, Beijing, 100049, PR China.
- Innovation Academy for Green Manufacture Chinese Academy of Sciences, Beijing, 100190, PR China.
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24
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Prudden H, Tatoud R, Slack C, Shattock R, Anklesaria P, Bekker LG, Buchbinder S. Experimental Medicine for HIV Vaccine Research and Development. Vaccines (Basel) 2023; 11:970. [PMID: 37243074 PMCID: PMC10222747 DOI: 10.3390/vaccines11050970] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Revised: 05/02/2023] [Accepted: 05/06/2023] [Indexed: 05/28/2023] Open
Abstract
The development of safe and effective HIV vaccines has been a scientific challenge for more than 40 years. Despite disappointing results from efficacy clinical trials, much has been learnt from years of research and development. In a rapidly evolving HIV prevention landscape, swift evaluation of multiple vaccine approaches eliciting cross-reactive humoral and cellular responses is needed to ensure the development of efficacious vaccine candidates. To contain increasing costs, innovative clinical research methods are required. Experimental medicine has the potential to accelerate vaccine discovery by iterating early stages of clinical testing faster and by selecting the most promising immunogen combinations for further clinical evaluation. As part of its mission to unite diverse stakeholders involved in the response to the HIV epidemic, the Global HIV Vaccine Enterprise at IAS-the International AIDS Society-hosted a series of online events between January and September 2022 to discuss the merits and challenges of experimental medicine studies to accelerate the development of safe and effective HIV vaccines. This report summarizes key questions and discussions across the series of events, which brought together scientists, policy makers, community stakeholders, advocates, bioethicists, and funders.
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Affiliation(s)
| | - Roger Tatoud
- Origena Consulting, 01210 Ferney Voltaire, France;
| | - Cathy Slack
- HIV/AIDS Vaccines Ethics Group (HAVEG), University of KwaZulu-Natal, Durban 4041, South Africa;
| | | | | | - Linda-Gail Bekker
- The Desmond Tutu HIV Centre, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa;
| | - Susan Buchbinder
- Bridge HIV, San Francisco Department of Public Health, San Francisco, CA 94102, USA;
- Department of Epidemiology and Biostatistics, University of California, San Francisco, CA 94158, USA
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25
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Verma SK, Mahajan P, Singh NK, Gupta A, Aggarwal R, Rappuoli R, Johri AK. New-age vaccine adjuvants, their development, and future perspective. Front Immunol 2023; 14:1043109. [PMID: 36911719 PMCID: PMC9998920 DOI: 10.3389/fimmu.2023.1043109] [Citation(s) in RCA: 84] [Impact Index Per Article: 42.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Accepted: 01/26/2023] [Indexed: 02/26/2023] Open
Abstract
In the present scenario, immunization is of utmost importance as it keeps us safe and protects us from infectious agents. Despite the great success in the field of vaccinology, there is a need to not only develop safe and ideal vaccines to fight deadly infections but also improve the quality of existing vaccines in terms of partial or inconsistent protection. Generally, subunit vaccines are known to be safe in nature, but they are mostly found to be incapable of generating the optimum immune response. Hence, there is a great possibility of improving the potential of a vaccine in formulation with novel adjuvants, which can effectively impart superior immunity. The vaccine(s) in formulation with novel adjuvants may also be helpful in fighting pathogens of high antigenic diversity. However, due to the limitations of safety and toxicity, very few human-compatible adjuvants have been approved. In this review, we mainly focus on the need for new and improved vaccines; the definition of and the need for adjuvants; the characteristics and mechanisms of human-compatible adjuvants; the current status of vaccine adjuvants, mucosal vaccine adjuvants, and adjuvants in clinical development; and future directions.
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Affiliation(s)
| | - Pooja Mahajan
- School of Life Sciences, Jawaharlal Nehru University, New Delhi, India
| | - Nikhlesh K. Singh
- Integrative Biosciences Center, Department of Ophthalmology, Visual and Anatomical Sciences, Wayne State University, School of Medicine, Detroit, MI, United States
| | - Ankit Gupta
- Microbiology Division, Defence Research and Development Establishment, Gwalior, India
| | - Rupesh Aggarwal
- School of Life Sciences, Jawaharlal Nehru University, New Delhi, India
| | | | - Atul Kumar Johri
- School of Life Sciences, Jawaharlal Nehru University, New Delhi, India
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26
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Yuan Y, Gao F, Chang Y, Zhao Q, He X. Advances of mRNA vaccine in tumor: a maze of opportunities and challenges. Biomark Res 2023; 11:6. [PMID: 36650562 PMCID: PMC9845107 DOI: 10.1186/s40364-023-00449-w] [Citation(s) in RCA: 35] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Accepted: 01/10/2023] [Indexed: 01/19/2023] Open
Abstract
High-frequency mutations in tumor genomes could be exploited as an asset for developing tumor vaccines. In recent years, with the tremendous breakthrough in genomics, intelligence algorithm, and in-depth insight of tumor immunology, it has become possible to rapidly target genomic alterations in tumor cell and rationally select vaccine targets. Among a variety of candidate vaccine platforms, the early application of mRNA was limited by instability low efficiency and excessive immunogenicity until the successful development of mRNA vaccines against SARS-COV-2 broken of technical bottleneck in vaccine preparation, allowing tumor mRNA vaccines to be prepared rapidly in an economical way with good performance of stability and efficiency. In this review, we systematically summarized the classification and characteristics of tumor antigens, the general process and methods for screening neoantigens, the strategies of vaccine preparations and advances in clinical trials, as well as presented the main challenges in the current mRNA tumor vaccine development.
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Affiliation(s)
- Yuan Yuan
- grid.413247.70000 0004 1808 0969Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China ,grid.412793.a0000 0004 1799 5032Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Fan Gao
- grid.413247.70000 0004 1808 0969Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China ,grid.412793.a0000 0004 1799 5032Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ying Chang
- grid.413247.70000 0004 1808 0969Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China ,grid.413247.70000 0004 1808 0969Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Diseases, Wuhan, China
| | - Qiu Zhao
- grid.413247.70000 0004 1808 0969Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China ,grid.413247.70000 0004 1808 0969Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Diseases, Wuhan, China
| | - Xingxing He
- grid.413247.70000 0004 1808 0969Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China ,grid.412793.a0000 0004 1799 5032Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China ,grid.413247.70000 0004 1808 0969Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Diseases, Wuhan, China
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27
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Wang Y, Wang X, Jia X, Li J, Fu J, Huang X, Cui X, Wang B, Luo W, Lin C, Li Z, Luu LDW, Li S, Zhu X, Tai J. Influenza vaccination features revealed by a single-cell transcriptome atlas. J Med Virol 2023; 95:e28174. [PMID: 36163452 DOI: 10.1002/jmv.28174] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Revised: 09/05/2022] [Accepted: 09/23/2022] [Indexed: 01/11/2023]
Abstract
Emerging and re-emerging viruses like influenza virus pose a continuous global public health threat. Vaccines are one of the most effective public health strategies for controlling infectious diseases. However, little is known about the immunological features of vaccination at the single-cell resolution, including for influenza vaccination. Here, we report the single-cell transcriptome atlas of longitudinally collected peripheral blood mononuclear cells (PBMCs) in individuals immunized with an inactivated influenza vaccine. Overall, vaccination with the influenza vaccine only had a small impact on the composition of peripheral immune cells, but elicited global transcriptional changes in multiple immune cell subsets. In plasma and B cell subsets, transcriptomic changes, which were mostly involved in antibody production as well as B cell activation and differentiation, were observed after influenza vaccinations. In influenza-vaccinated individuals, we found a reduction in multiple biological processes (e.g., interferon response, inflammatory response, HLA-I/II molecules, cellular apoptosis, migration, and cytotoxicity, etc.,) 7 days postvaccination in multiple immune cell subsets. However, 14 days postvaccination, these levels returned to similar levels observed in prevaccination samples. Additionally, we did not observe significant upregulation of pro-inflammatory response genes and key thrombosis-related genes in influenza-vaccinated individuals. Taken together, we report a cell atlas of the peripheral immune response to influenza vaccination and provide a resource for understanding the immunological response mechanisms of influenza vaccination.
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Affiliation(s)
- Yi Wang
- Experimental Research Center, Capital Institute of Pediatrics, Beijing, P. R. China
| | - Xiaoxia Wang
- Central & Clinical Laboratory of Sanya People's Hospital, Sanya, Hainan, P. R. China
| | - Xinbei Jia
- Department of Otolaryngology Head and Neck Surgery, Children's Hospital Capital Institute of Pediatrics, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P. R. China
| | - Jieqiong Li
- Department of Respiratory Disease, National Center for Children's Health, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, P. R. China
| | - Jin Fu
- Experimental Research Center, Capital Institute of Pediatrics, Beijing, P. R. China
| | - Xiaolan Huang
- Experimental Research Center, Capital Institute of Pediatrics, Beijing, P. R. China
| | - Xiaodai Cui
- Experimental Research Center, Capital Institute of Pediatrics, Beijing, P. R. China
| | - Bike Wang
- Prevention and Health Care of Sanya People's Hospital, Sanya, Hainan, P. R. China
| | - Wenkai Luo
- Central & Clinical Laboratory of Sanya People's Hospital, Sanya, Hainan, P. R. China
| | - Chengcong Lin
- Prevention and Health Care of Sanya People's Hospital, Sanya, Hainan, P. R. China
| | - Zhenjun Li
- State Key Laboratory for Infectious Disease Prevention and Control, Chinese Center for Disease Control and Prevention, National Institute for Communicable Disease Control and Prevention, Beijing, P.R. China
| | - Laurence Don Wai Luu
- School of Life Sciences, University of Technology Sydney, Sydney, New South Wales, Australia
| | - Shijun Li
- Laboratory of Infectious Disease of Experimental Center, Guizhou Provincial Center for Disease Control and Prevention, Guiyang, P. R. China
| | - Xiong Zhu
- Central & Clinical Laboratory of Sanya People's Hospital, Sanya, Hainan, P. R. China
| | - Jun Tai
- Department of Otolaryngology Head and Neck Surgery, Children's Hospital Capital Institute of Pediatrics, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P. R. China
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28
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Gao Y, Wang W, Yang Y, Zhao Q, Yang C, Jia X, Liu Y, Zhou M, Zeng W, Huang X, Chiu S, Jin T, Wu X. Developing Next-Generation Protein-Based Vaccines Using High-Affinity Glycan Ligand-Decorated Glyconanoparticles. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2023; 10:e2204598. [PMID: 36398611 PMCID: PMC9839878 DOI: 10.1002/advs.202204598] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Revised: 10/13/2022] [Indexed: 06/16/2023]
Abstract
Major diseases, such as cancer and COVID-19, are frightening global health problems, and sustained action is necessary to develop vaccines. Here, for the first time, ethoxy acetalated dextran nanoparticles (Ace-Dex-NPs) are functionalized with 9-N-(4H-thieno[3,2-c]chromene-2-carbamoyl)-Siaα2-3Galβ1-4GlcNAc (TCC Sia-LacNAc) targeting macrophages as a universal vaccine design platform. First, azide-containing oxidized Ace-Dex-NPs are synthesized. After the NPs are conjugated with ovalbumin (OVA) and resiquimod (Rd), they are coupled to TCC Sia-LacNAc-DBCO to produce TCC Sia-Ace-Dex-OVA-Rd, which induce a potent, long-lasting OVA-specific cytotoxic T-lymphocyte (CTL) response and high anti-OVA IgG, providing mice with superior protection against tumors. Next, this strategy is exploited to develop vaccines against infection by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein is the main target for neutralizing antibodies. The TCC Sia-Ace-Dex platform is preferentially used for designing an RBD-based vaccine. Strikingly, the synthetic TCC Sia-Ace-Dex-RBD-Rd elicited potent RBD-neutralizing antibodies against live SARS-CoV-2 infected Vero E6 cells. To develop a universal SARS-CoV-2 vaccine, the TCC Sia-Ace-Dex-N-Rd vaccine carrying SARS-CoV-2 nucleocapsid protein (N) is also prepared, which is highly conserved among SARS-CoV-2 and its variants of concern (VOCs), including Omicron (BA.1 to BA.5); this vaccine can trigger strong N-specific CTL responses against target cells infected with SARS-CoV-2 and its VOCs.
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Affiliation(s)
- Yanan Gao
- National Glycoengineering Research CenterShandong Key Laboratory of Carbohydrate Chemistry and GlycobiologyNMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate‐based MedicineShandong UniversityQingdaoShandong266237China
| | - Wei Wang
- State Key Laboratory of VirologyWuhan Institute of VirologyCenter for Biosafety Mega‐ScienceChinese Academy of SciencesWuhan430071China
- University of the Chinese Academy of SciencesBeijing100049China
| | - Yunru Yang
- Department of Basic Medical SciencesDivision of Molecular MedicineDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui230001China
| | - Qingyu Zhao
- National Glycoengineering Research CenterShandong Key Laboratory of Carbohydrate Chemistry and GlycobiologyNMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate‐based MedicineShandong UniversityQingdaoShandong266237China
| | - Chendong Yang
- National Glycoengineering Research CenterShandong Key Laboratory of Carbohydrate Chemistry and GlycobiologyNMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate‐based MedicineShandong UniversityQingdaoShandong266237China
| | - Xiaoying Jia
- State Key Laboratory of VirologyWuhan Institute of VirologyCenter for Biosafety Mega‐ScienceChinese Academy of SciencesWuhan430071China
- University of the Chinese Academy of SciencesBeijing100049China
| | - Yang Liu
- State Key Laboratory of VirologyWuhan Institute of VirologyCenter for Biosafety Mega‐ScienceChinese Academy of SciencesWuhan430071China
| | - Minmin Zhou
- State Key Laboratory of VirologyWuhan Institute of VirologyCenter for Biosafety Mega‐ScienceChinese Academy of SciencesWuhan430071China
- University of the Chinese Academy of SciencesBeijing100049China
| | - Weihong Zeng
- Department of Basic Medical SciencesDivision of Molecular MedicineDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui230001China
| | - Xuefei Huang
- Departments of Chemistry and Biomedical EngineeringInstitute for Quantitative Health Science and EngineeringMichigan State UniversityEast LansingMichigan48824United States
| | - Sandra Chiu
- Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui230001China
| | - Tengchuan Jin
- Department of Basic Medical SciencesDivision of Molecular MedicineDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui230001China
| | - Xuanjun Wu
- National Glycoengineering Research CenterShandong Key Laboratory of Carbohydrate Chemistry and GlycobiologyNMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate‐based MedicineShandong UniversityQingdaoShandong266237China
- Suzhou Research InstituteShandong UniversitySuzhouJiangsu215123China
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Salod Z, Mahomed O. Protocol for a scoping review of potential vaccine candidates predicted by VaxiJen for different viral pathogens between 2017-2021. Syst Rev 2022; 11:284. [PMID: 36585703 PMCID: PMC9801145 DOI: 10.1186/s13643-022-02121-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Accepted: 11/03/2022] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND Vaccination is essential for the prevention of infectious diseases and has helped to reduce disease-related mortality, such as pneumonia. However, traditional vaccine development is time-consuming and risky. Reverse vaccinology (RV) is a promising alternative to developing vaccines based on the in silico discovery of antigens, often termed 'potential vaccine candidates' (PVCs), using a pathogen's proteome. RV prediction technologies, such as VaxiJen (founded in 2007), are used to take the first step toward vaccine development. VaxiJen is used by researchers to identify PVCs for various diseases. A 10-year review of these PVCs was published in 2017. There has since been no review of viral PVCs predicted by VaxiJen from 2017 to 2021. The proposed scoping review aims to address this gap. METHODS This protocol is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) 2015 checklist. The review will employ Arksey and O'Malley's five-stage methodological framework, which was later enhanced by Levac et al. and the Joanna Briggs Institute (JBI). The PRISMA extension for Scoping Reviews (PRISMA-ScR) reporting guideline will be utilized with this framework. PubMed, Scopus, Web of Science, EBSCOhost, and ProQuest One Academic will be searched using the term 'vaxijen'. The inclusion criteria will be English-only full-text original articles published in peer-reviewed journals and unpublished papers from 2017 to 2021. Rayyan will be used to deduplicate, screen titles and abstracts of articles. The articles' full texts will be examined. The data will be extracted using Microsoft Excel. Using a data charting form, data will be sifted and organized by key categories and themes. DISCUSSION This protocol was submitted for publication and went through an extensive peer review process. The review has implications for novel vaccine development against various viruses. The key limitation of this study is language bias due to the selection of English-only papers because of limited resources. This study will not require ethical clearance since it will use secondary data and will not include patients. Nevertheless, this research is part of a larger project that was submitted for ethical consideration to the Biomedical Research Ethics Committee of the University of KwaZulu-Natal in South Africa. This study's findings will be published in a peer-reviewed journal and provided to relevant stakeholders. SYSTEMATIC REVIEW REGISTRATION Open Science Framework (OSF): https://osf.io/ht8wr.
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Affiliation(s)
- Zakia Salod
- Discipline of Public Health Medicine, School of Nursing and Public Health, University of KwaZulu-Natal, Durban, KwaZulu-Natal South Africa
| | - Ozayr Mahomed
- Discipline of Public Health Medicine, School of Nursing and Public Health, University of KwaZulu-Natal, Durban, KwaZulu-Natal South Africa
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Huang S, Zhu Y, Zhang L, Zhang Z. Recent Advances in Delivery Systems for Genetic and Other Novel Vaccines. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2022; 34:e2107946. [PMID: 34914144 DOI: 10.1002/adma.202107946] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Revised: 12/11/2021] [Indexed: 06/14/2023]
Abstract
Vaccination is one of the most successful and cost-effective prophylactic measures against diseases, especially infectious diseases including smallpox and polio. However, the development of effective prophylactic or therapeutic vaccines for other diseases such as cancer remains challenging. This is often due to the imprecise control of vaccine activity in vivo which leads to insufficient/inappropriate immune responses or short immune memory. The development of new vaccine types in recent decades has created the potential for improving the protective potency against these diseases. Genetic and subunit vaccines are two major categories of these emerging vaccines. Owing to their nature, they rely heavily on delivery systems with various functions, such as effective cargo protection, immunogenicity enhancement, targeted delivery, sustained release of antigens, selective activation of humoral and/or cellular immune responses against specific antigens, and reduced adverse effects. Therefore, vaccine delivery systems may significantly affect the final outcome of genetic and other novel vaccines and are vital for their development. This review introduces these studies based on their research emphasis on functional design or administration route optimization, presents recent progress, and discusses features of new vaccine delivery systems, providing an overview of this field.
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Affiliation(s)
- Shiqi Huang
- Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, College of Polymer Science and Engineering, Sichuan University, Chengdu, 610041, P. R. China
| | - Yining Zhu
- Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, College of Polymer Science and Engineering, Sichuan University, Chengdu, 610041, P. R. China
| | - Ling Zhang
- Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, College of Polymer Science and Engineering, Sichuan University, Chengdu, 610041, P. R. China
| | - Zhirong Zhang
- Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, College of Polymer Science and Engineering, Sichuan University, Chengdu, 610041, P. R. China
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Salod Z, Mahomed O. Mapping Potential Vaccine Candidates Predicted by VaxiJen for Different Viral Pathogens between 2017-2021-A Scoping Review. Vaccines (Basel) 2022; 10:1785. [PMID: 36366294 PMCID: PMC9695814 DOI: 10.3390/vaccines10111785] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Revised: 10/16/2022] [Accepted: 10/18/2022] [Indexed: 09/29/2023] Open
Abstract
Reverse vaccinology (RV) is a promising alternative to traditional vaccinology. RV focuses on in silico methods to identify antigens or potential vaccine candidates (PVCs) from a pathogen's proteome. Researchers use VaxiJen, the most well-known RV tool, to predict PVCs for various pathogens. The purpose of this scoping review is to provide an overview of PVCs predicted by VaxiJen for different viruses between 2017 and 2021 using Arksey and O'Malley's framework and the Preferred Reporting Items for Systematic Reviews extension for Scoping Reviews (PRISMA-ScR) guidelines. We used the term 'vaxijen' to search PubMed, Scopus, Web of Science, EBSCOhost, and ProQuest One Academic. The protocol was registered at the Open Science Framework (OSF). We identified articles on this topic, charted them, and discussed the key findings. The database searches yielded 1033 articles, of which 275 were eligible. Most studies focused on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), published between 2020 and 2021. Only a few articles (8/275; 2.9%) conducted experimental validations to confirm the predictions as vaccine candidates, with 2.2% (6/275) articles mentioning recombinant protein expression. Researchers commonly targeted parts of the SARS-CoV-2 spike (S) protein, with the frequently predicted epitopes as PVCs being major histocompatibility complex (MHC) class I T cell epitopes WTAGAAAYY, RQIAPGQTG, IAIVMVTIM, and B cell epitope IAPGQTGKIADY, among others. The findings of this review are promising for the development of novel vaccines. We recommend that vaccinologists use these findings as a guide to performing experimental validation for various viruses, with SARS-CoV-2 as a priority, because better vaccines are needed, especially to stay ahead of the emergence of new variants. If successful, these vaccines could provide broader protection than traditional vaccines.
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Affiliation(s)
- Zakia Salod
- Discipline of Public Health Medicine, University of KwaZulu-Natal, Durban 4051, South Africa
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Dowling DJ, Barman S, Smith AJ, Borriello F, Chaney D, Brightman SE, Melhem G, Brook B, Menon M, Soni D, Schüller S, Siram K, Nanishi E, Bazin HG, Burkhart DJ, Levy O, Evans JT. Development of a TLR7/8 agonist adjuvant formulation to overcome early life hyporesponsiveness to DTaP vaccination. Sci Rep 2022; 12:16860. [PMID: 36258023 PMCID: PMC9579132 DOI: 10.1038/s41598-022-20346-w] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Accepted: 09/12/2022] [Indexed: 12/02/2022] Open
Abstract
Infection is the most common cause of mortality early in life, yet the broad potential of immunization is not fully realized in this vulnerable population. Most vaccines are administered during infancy and childhood, but in some cases the full benefit of vaccination is not realized in-part. New adjuvants are cardinal to further optimize current immunization approaches for early life. However, only a few classes of adjuvants are presently incorporated in vaccines approved for human use. Recent advances in the discovery and delivery of Toll-like receptor (TLR) agonist adjuvants have provided a new toolbox for vaccinologists. Prominent among these candidate adjuvants are synthetic small molecule TLR7/8 agonists. The development of an effective infant Bordetella pertussis vaccine is urgently required because of the resurgence of pertussis in many countries, contemporaneous to the switch from whole cell to acellular vaccines. In this context, TLR7/8 adjuvant based vaccine formulation strategies may be a promising tool to enhance and accelerate early life immunity by acellular B. pertussis vaccines. In the present study, we optimized (a) the formulation delivery system, (b) structure, and (c) immunologic activity of novel small molecule imidazoquinoline TLR7/8 adjuvants towards human infant leukocytes, including dendritic cells. Upon immunization of neonatal mice, this TLR7/8 adjuvant overcame neonatal hyporesponsiveness to acellular pertussis vaccination by driving a T helper (Th)1/Th17 biased T cell- and IgG2c-skewed humoral response to a licensed acellular vaccine (DTaP). This potent immunization strategy may represent a new paradigm for effective immunization against pertussis and other pathogens in early life.
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Affiliation(s)
- David J Dowling
- Precision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital, Harvard Institutes of Medicine, Room 842, 4 Blackfan Circle, Boston, MA, 02115, USA
- Harvard Medical School, Boston, MA, USA
| | - Soumik Barman
- Precision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital, Harvard Institutes of Medicine, Room 842, 4 Blackfan Circle, Boston, MA, 02115, USA
- Harvard Medical School, Boston, MA, USA
| | - Alyson J Smith
- Center for Translational Medicine, University of Montana, 32 Campus Drive, Missoula, MT, 59802, USA
- Seagen, Bothell, WA, USA
| | - Francesco Borriello
- Precision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital, Harvard Institutes of Medicine, Room 842, 4 Blackfan Circle, Boston, MA, 02115, USA
- Harvard Medical School, Boston, MA, USA
- Department of Translational Medical Sciences, Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, 80131, Italy
- WAO Center of Excellence, Naples, 80131, Italy
- Generate Biomedicines, Cambridge, MA, USA
| | - Danielle Chaney
- Precision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital, Harvard Institutes of Medicine, Room 842, 4 Blackfan Circle, Boston, MA, 02115, USA
- Harvard Medical School, Boston, MA, USA
| | - Spencer E Brightman
- Precision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital, Harvard Institutes of Medicine, Room 842, 4 Blackfan Circle, Boston, MA, 02115, USA
| | - Gandolina Melhem
- Precision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital, Harvard Institutes of Medicine, Room 842, 4 Blackfan Circle, Boston, MA, 02115, USA
| | - Byron Brook
- Precision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital, Harvard Institutes of Medicine, Room 842, 4 Blackfan Circle, Boston, MA, 02115, USA
- Harvard Medical School, Boston, MA, USA
| | - Manisha Menon
- Precision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital, Harvard Institutes of Medicine, Room 842, 4 Blackfan Circle, Boston, MA, 02115, USA
| | - Dheeraj Soni
- Precision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital, Harvard Institutes of Medicine, Room 842, 4 Blackfan Circle, Boston, MA, 02115, USA
- Harvard Medical School, Boston, MA, USA
| | - Simone Schüller
- Precision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital, Harvard Institutes of Medicine, Room 842, 4 Blackfan Circle, Boston, MA, 02115, USA
- Harvard Medical School, Boston, MA, USA
| | - Karthik Siram
- Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, MT, USA
| | - Etsuro Nanishi
- Precision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital, Harvard Institutes of Medicine, Room 842, 4 Blackfan Circle, Boston, MA, 02115, USA
- Harvard Medical School, Boston, MA, USA
| | - Hélène G Bazin
- Center for Translational Medicine, University of Montana, 32 Campus Drive, Missoula, MT, 59802, USA
- Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, MT, USA
| | - David J Burkhart
- Center for Translational Medicine, University of Montana, 32 Campus Drive, Missoula, MT, 59802, USA
- Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, MT, USA
| | - Ofer Levy
- Precision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital, Harvard Institutes of Medicine, Room 842, 4 Blackfan Circle, Boston, MA, 02115, USA.
- Harvard Medical School, Boston, MA, USA.
- Broad Institute of MIT & Harvard, Cambridge, MA, USA.
| | - Jay T Evans
- Center for Translational Medicine, University of Montana, 32 Campus Drive, Missoula, MT, 59802, USA.
- Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, MT, USA.
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Prochetto E, Borgna E, Jiménez-Cortegana C, Sánchez-Margalet V, Cabrera G. Myeloid-derived suppressor cells and vaccination against pathogens. Front Cell Infect Microbiol 2022; 12:1003781. [PMID: 36250061 PMCID: PMC9557202 DOI: 10.3389/fcimb.2022.1003781] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Accepted: 09/15/2022] [Indexed: 12/01/2022] Open
Abstract
It is widely accepted that the immune system includes molecular and cellular components that play a role in regulating and suppressing the effector immune response in almost any process in which the immune system is involved. Myeloid-derived suppressor cells (MDSCs) are described as a heterogeneous population of myeloid origin, immature state, with a strong capacity to suppress T cells and other immune populations. Although the initial characterization of these cells was strongly associated with pathological conditions such as cancer and then with chronic and acute infections, extensive evidence supports that MDSCs are also involved in physiological/non-pathological settings, including pregnancy, neonatal period, aging, and vaccination. Vaccination is one of the greatest public health achievements and has reduced mortality and morbidity caused by many pathogens. The primary goal of prophylactic vaccination is to induce protection against a potential pathogen by mimicking, at least in a part, the events that take place during its natural interaction with the host. This strategy allows the immune system to prepare humoral and cellular effector components to cope with the real infection. This approach has been successful in developing vaccines against many pathogens. However, when the infectious agents can evade and subvert the host immune system, inducing cells with regulatory/suppressive capacity, the development of vaccines may not be straightforward. Notably, there is a long list of complex pathogens that can expand MDSCs, for which a vaccine is still not available. Moreover, vaccination against numerous bacteria, viruses, parasites, and fungi has also been shown to cause MDSC expansion. Increases are not due to a particular adjuvant or immunization route; indeed, numerous adjuvants and immunization routes have been reported to cause an accumulation of this immunosuppressive population. Most of the reports describe that, according to their suppressive nature, MDSCs may limit vaccine efficacy. Taking into account the accumulated evidence supporting the involvement of MDSCs in vaccination, this review aims to compile the studies that highlight the role of MDSCs during the assessment of vaccines against pathogens.
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Affiliation(s)
- Estefanía Prochetto
- Laboratorio de Tecnología Inmunológica, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe capital, Argentina
| | - Eliana Borgna
- Laboratorio de Tecnología Inmunológica, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe capital, Argentina
| | - Carlos Jiménez-Cortegana
- Clinical Laboratory, Department of Medical Biochemistry, Molecular Biology and Immunology, School of Medicine, Virgen Macarena University Hospital, University of Seville, Seville, Spain
| | - Víctor Sánchez-Margalet
- Clinical Laboratory, Department of Medical Biochemistry, Molecular Biology and Immunology, School of Medicine, Virgen Macarena University Hospital, University of Seville, Seville, Spain
| | - Gabriel Cabrera
- Laboratorio de Tecnología Inmunológica, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe capital, Argentina
- *Correspondence: Gabriel Cabrera,
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Deng JZ, Lin J, Chen M, Lancaster C, Zhuang P. Characterization of High Molecular Weight Pneumococcal Conjugate by SEC-MALS and AF4-MALS. Polymers (Basel) 2022; 14:3769. [PMID: 36145915 PMCID: PMC9501040 DOI: 10.3390/polym14183769] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Revised: 09/06/2022] [Accepted: 09/06/2022] [Indexed: 11/25/2022] Open
Abstract
Infections by Streptococcus pneumoniae can cause serious pneumococcal diseases and other medical complications among patients. Polysaccharide-based vaccines have been successfully developed as prophylactic agents against such deadly bacterial infections. In the 1980s, PNEUMOVAX® 23 were introduced as the first pneumococcal polysaccharide vaccines (PPSV). Later, pneumococcal polysaccharides were conjugated to a carrier protein to improve immune responses. Pneumococcal conjugate vaccines (PCV) such as PREVNAR® and VAXNEUVANCE™ have been developed. Of the more than 90 pneumococcal bacteria serotypes, serotype 1 (ST-1) and serotype 4 (ST-4) are the two main types that cause invasive pneumococcal diseases (IPD) that could lead to morbidity and mortality. Development of a novel multi-valent PCV against these serotypes requires extensive biophysical and biochemical characterizations of each monovalent conjugate (MVC) in the vaccine. To understand and characterize these high molecular weight (Mw) polysaccharide protein conjugates, we employed the multi-angle light scattering (MALS) technique coupled with size-exclusion chromatography (SEC) separation and asymmetrical flow field flow fractionation (AF4). MALS analysis of MVCs from the two orthogonal separation mechanisms helps shed light on the heterogeneity in conformation and aggregation states of each conjugate.
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Affiliation(s)
- James Z. Deng
- Vaccine Analytical Research & Development, Merck & Co., Inc., Rahway, NJ 07065, USA
| | - Jason Lin
- Wyatt Technology Corporation, Goleta, CA 93117, USA
| | | | - Catherine Lancaster
- Vaccine Analytical Research & Development, Merck & Co., Inc., Rahway, NJ 07065, USA
| | - Ping Zhuang
- Vaccine Analytical Research & Development, Merck & Co., Inc., Rahway, NJ 07065, USA
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Smart combination of aluminum hydroxide and MF59 to induce strong cellular immune responses. J Control Release 2022; 349:699-711. [PMID: 35907590 DOI: 10.1016/j.jconrel.2022.07.032] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Revised: 07/19/2022] [Accepted: 07/24/2022] [Indexed: 11/20/2022]
Abstract
As two of the most widely used adjuvants, aluminum hydroxide and the oil-in-water emulsion MF59 have their intrinsic limitations: classical aluminum gel induces only weak cellular immune responses while MF59 cannot be used as an antigen delivery system due to its poor physical interaction with antigen molecules. Herein, we combined these two adjuvants and constructed a novel nano-vaccine delivery system by inserting aluminum hydroxide into the surface of a modified MF59 nano-emulsion (AlNEs). A model antigen ovalbumin (OVA) and an immune potentiator CpG were adsorbed on the surface of AlNEs (hereinafter AlNEs-OVA-CpG) through a facile mixing step. After subcutaneous injection, AlNEs-OVA-CpG effectively drained to lymph nodes, delivered both cargos into lymph node-resident antigen presenting cells (APCs), and escaped from lysosomes into the cytoplasm, resulting in enhanced antigen cross-presentation. Finally, AlNEs-OVA-CpG induced potent antigen-specific humoral and cellular immune responses, which significantly inhibited tumor growth and prolonged mice survival in a EG7-OVA tumor model. In sum, our results suggested that AlNEs have a great prospect to induce CD8+ T cell responses for subunit antigens.
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Brooks BD, Beland A, Aguero G, Taylor N, Towne FD. Moving beyond Titers. Vaccines (Basel) 2022; 10:vaccines10050683. [PMID: 35632439 PMCID: PMC9144832 DOI: 10.3390/vaccines10050683] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Revised: 04/18/2022] [Accepted: 04/20/2022] [Indexed: 01/27/2023] Open
Abstract
Vaccination to prevent and even eliminate disease is amongst the greatest achievements of modern medicine. Opportunities remain in vaccine development to improve protection across the whole population. A next step in vaccine development is the detailed molecular characterization of individual humoral immune responses against a pathogen, especially the rapidly evolving pathogens. New technologies such as sequencing the immune repertoire in response to disease, immunogenomics/vaccinomics, particularly the individual HLA variants, and high-throughput epitope characterization offer new insights into disease protection. Here, we highlight the emerging technologies that could be used to identify variation within the human population, facilitate vaccine discovery, improve vaccine safety and efficacy, and identify mechanisms of generating immunological memory. In today’s vaccine-hesitant climate, these techniques used individually or especially together have the potential to improve vaccine effectiveness and safety and thus vaccine uptake rates. We highlight the importance of using these techniques in combination to understand the humoral immune response as a whole after vaccination to move beyond neutralizing titers as the standard for immunogenicity and vaccine efficacy, especially in clinical trials.
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Affiliation(s)
- Benjamin D. Brooks
- Department of Biomedical Sciences, Rocky Vista University, Ivins, UT 84738, USA
- Inovan Inc., Fargo, ND 58103, USA
- Correspondence: ; Tel.: +1-(435)-222-1304
| | - Alexander Beland
- College of Osteopathic Medicine, Rocky Vista University, Parker, CO 80112, USA; (A.B.); (G.A.); (N.T.); (F.D.T.)
| | - Gabriel Aguero
- College of Osteopathic Medicine, Rocky Vista University, Parker, CO 80112, USA; (A.B.); (G.A.); (N.T.); (F.D.T.)
| | - Nicholas Taylor
- College of Osteopathic Medicine, Rocky Vista University, Parker, CO 80112, USA; (A.B.); (G.A.); (N.T.); (F.D.T.)
| | - Francina D. Towne
- College of Osteopathic Medicine, Rocky Vista University, Parker, CO 80112, USA; (A.B.); (G.A.); (N.T.); (F.D.T.)
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Barman S, Soni D, Brook B, Nanishi E, Dowling DJ. Precision Vaccine Development: Cues From Natural Immunity. Front Immunol 2022; 12:662218. [PMID: 35222350 PMCID: PMC8866702 DOI: 10.3389/fimmu.2021.662218] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2021] [Accepted: 12/21/2021] [Indexed: 12/31/2022] Open
Abstract
Traditional vaccine development against infectious diseases has been guided by the overarching aim to generate efficacious vaccines normally indicated by an antibody and/or cellular response that correlates with protection. However, this approach has been shown to be only a partially effective measure, since vaccine- and pathogen-specific immunity may not perfectly overlap. Thus, some vaccine development strategies, normally focused on targeted generation of both antigen specific antibody and T cell responses, resulting in a long-lived heterogenous and stable pool of memory lymphocytes, may benefit from better mimicking the immune response of a natural infection. However, challenges to achieving this goal remain unattended, due to gaps in our understanding of human immunity and full elucidation of infectious pathogenesis. In this review, we describe recent advances in the development of effective vaccines, focusing on how understanding the differences in the immunizing and non-immunizing immune responses to natural infections and corresponding shifts in immune ontogeny are crucial to inform the next generation of infectious disease vaccines.
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Affiliation(s)
- Soumik Barman
- Precision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital, Boston, MA, United States.,Department of Pediatrics, Harvard Medical School, Boston, MA, United States
| | - Dheeraj Soni
- Precision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital, Boston, MA, United States.,Department of Pediatrics, Harvard Medical School, Boston, MA, United States
| | - Byron Brook
- Precision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital, Boston, MA, United States.,Department of Pediatrics, Harvard Medical School, Boston, MA, United States
| | - Etsuro Nanishi
- Precision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital, Boston, MA, United States.,Department of Pediatrics, Harvard Medical School, Boston, MA, United States
| | - David J Dowling
- Precision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital, Boston, MA, United States.,Department of Pediatrics, Harvard Medical School, Boston, MA, United States
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38
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Firdaus FZ, Skwarczynski M, Toth I. Developments in Vaccine Adjuvants. METHODS IN MOLECULAR BIOLOGY (CLIFTON, N.J.) 2022; 2412:145-178. [PMID: 34918245 DOI: 10.1007/978-1-0716-1892-9_8] [Citation(s) in RCA: 56] [Impact Index Per Article: 18.7] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Vaccines, including subunit, recombinant, and conjugate vaccines, require the use of an immunostimulator/adjuvant for maximum efficacy. Adjuvants not only enhance the strength and longevity of immune responses but may also influence the type of response. In this chapter, we review the adjuvants that are available for use in human vaccines, such as alum, MF59, AS03, and AS01. We extensively discuss their composition, characteristics, mechanism of action, and effects on the immune system. Additionally, we summarize recent trends in adjuvant discovery, providing a brief overview of saponins, TLRs agonists, polysaccharides, nanoparticles, cytokines, and mucosal adjuvants.
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Affiliation(s)
- Farrhana Ziana Firdaus
- School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, Australia
| | - Mariusz Skwarczynski
- School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, Australia
| | - Istvan Toth
- School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, Australia. .,Institute of Molecular Biosciences, The University of Queensland, St Lucia, QLD, Australia. .,School of Pharmacy, The University of Queensland, Woolloongabba, QLD, Australia.
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39
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A novel STING agonist-adjuvanted pan-sarbecovirus vaccine elicits potent and durable neutralizing antibody and T cell responses in mice, rabbits and NHPs. Cell Res 2022; 32:269-287. [PMID: 35046518 PMCID: PMC8767042 DOI: 10.1038/s41422-022-00612-2] [Citation(s) in RCA: 67] [Impact Index Per Article: 22.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2021] [Accepted: 01/03/2022] [Indexed: 12/23/2022] Open
Abstract
The emergence of SARS-CoV-2 variants and potentially other highly pathogenic sarbecoviruses in the future highlights the need for pan-sarbecovirus vaccines. Here, we discovered a new STING agonist, CF501, and found that CF501-adjuvanted RBD-Fc vaccine (CF501/RBD-Fc) elicited significantly stronger neutralizing antibody (nAb) and T cell responses than Alum- and cGAMP-adjuvanted RBD-Fc in mice. Vaccination of rabbits and rhesus macaques (nonhuman primates, NHPs) with CF501/RBD-Fc elicited exceptionally potent nAb responses against SARS-CoV-2 and its nine variants and 41 S-mutants, SARS-CoV and bat SARSr-CoVs. CF501/RBD-Fc-immunized hACE2-transgenic mice were almost completely protected against SARS-CoV-2 challenge, even 6 months after the initial immunization. NHPs immunized with a single dose of CF501/RBD-Fc produced high titers of nAbs. The immunized macaques also exhibited durable humoral and cellular immune responses and showed remarkably reduced viral load in the upper and lower airways upon SARS-CoV-2 challenge even at 108 days post the final immunization. Thus, CF501/RBD-Fc can be further developed as a novel pan-sarbecovirus vaccine to combat current and future outbreaks of sarbecovirus diseases.
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40
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Roth GA, Picece VCTM, Ou BS, Luo W, Pulendran B, Appel EA. Designing spatial and temporal control of vaccine responses. NATURE REVIEWS. MATERIALS 2022; 7:174-195. [PMID: 34603749 PMCID: PMC8477997 DOI: 10.1038/s41578-021-00372-2] [Citation(s) in RCA: 174] [Impact Index Per Article: 58.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Accepted: 07/08/2021] [Indexed: 05/02/2023]
Abstract
Vaccines are the key technology to combat existing and emerging infectious diseases. However, increasing the potency, quality and durability of the vaccine response remains a challenge. As our knowledge of the immune system deepens, it becomes clear that vaccine components must be in the right place at the right time to orchestrate a potent and durable response. Material platforms, such as nanoparticles, hydrogels and microneedles, can be engineered to spatially and temporally control the interactions of vaccine components with immune cells. Materials-based vaccination strategies can augment the immune response by improving innate immune cell activation, creating local inflammatory niches, targeting lymph node delivery and controlling the time frame of vaccine delivery, with the goal of inducing enhanced memory immunity to protect against future infections. In this Review, we highlight the biological mechanisms underlying strong humoral and cell-mediated immune responses and explore materials design strategies to manipulate and control these mechanisms.
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Affiliation(s)
- Gillie A. Roth
- Department of Bioengineering, Stanford University, Stanford, CA USA
| | - Vittoria C. T. M. Picece
- Department of Materials Science & Engineering, Stanford University, Stanford, CA USA
- Department of Chemistry and Applied Biosciences, ETH Zürich, Zürich, Switzerland
| | - Ben S. Ou
- Department of Bioengineering, Stanford University, Stanford, CA USA
| | - Wei Luo
- Institute for Immunity, Transplantation & Infection, Stanford University School of Medicine, Stanford, CA USA
| | - Bali Pulendran
- Institute for Immunity, Transplantation & Infection, Stanford University School of Medicine, Stanford, CA USA
- ChEM-H Institute, Stanford University, Stanford, CA USA
- Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA USA
- Program in Immunology, Stanford University School of Medicine, Stanford, CA USA
- Department of Pathology, Stanford University School of Medicine, Stanford, CA USA
| | - Eric A. Appel
- Department of Bioengineering, Stanford University, Stanford, CA USA
- Department of Materials Science & Engineering, Stanford University, Stanford, CA USA
- ChEM-H Institute, Stanford University, Stanford, CA USA
- Department of Paediatrics — Endocrinology, Stanford University School of Medicine, Stanford, CA USA
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41
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Ghattas M, Dwivedi G, Lavertu M, Alameh MG. Vaccine Technologies and Platforms for Infectious Diseases: Current Progress, Challenges, and Opportunities. Vaccines (Basel) 2021; 9:1490. [PMID: 34960236 PMCID: PMC8708925 DOI: 10.3390/vaccines9121490] [Citation(s) in RCA: 88] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Revised: 12/02/2021] [Accepted: 12/11/2021] [Indexed: 01/09/2023] Open
Abstract
Vaccination is a key component of public health policy with demonstrated cost-effective benefits in protecting both human and animal populations. Vaccines can be manufactured under multiple forms including, inactivated (killed), toxoid, live attenuated, Virus-like Particles, synthetic peptide, polysaccharide, polysaccharide conjugate (glycoconjugate), viral vectored (vector-based), nucleic acids (DNA and mRNA) and bacterial vector/synthetic antigen presenting cells. Several processes are used in the manufacturing of vaccines and recent developments in medical/biomedical engineering, biology, immunology, and vaccinology have led to the emergence of innovative nucleic acid vaccines, a novel category added to conventional and subunit vaccines. In this review, we have summarized recent advances in vaccine technologies and platforms focusing on their mechanisms of action, advantages, and possible drawbacks.
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Affiliation(s)
- Majed Ghattas
- Department of Chemical Engineering, Polytechnique Montreal, Montreal, QC H3T 1J4, Canada;
- Institute of Biomedical Engineering, Polytechnique Montreal, Montreal, QC H3T 1J4, Canada
| | - Garima Dwivedi
- Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA;
| | - Marc Lavertu
- Department of Chemical Engineering, Polytechnique Montreal, Montreal, QC H3T 1J4, Canada;
- Institute of Biomedical Engineering, Polytechnique Montreal, Montreal, QC H3T 1J4, Canada
| | - Mohamad-Gabriel Alameh
- Division of Infectious Diseases, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
- AexeRNA Therapeutics, Washington, DC 20001, USA
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Kovalchik K, Hamelin D, Caron E. Generation of HLA Allele-Specific Spectral Libraries to Identify and Quantify Immunopeptidomes by SWATH/DIA-MS. METHODS IN MOLECULAR BIOLOGY (CLIFTON, N.J.) 2021; 2420:137-147. [PMID: 34905171 DOI: 10.1007/978-1-0716-1936-0_11] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
Developing a deep and comprehensive understanding of the collection of peptides presented by class I human leukocyte antigens (HLA ), collectively referred to as the immunopeptidome , is conducive to the success of a wide range of immunotherapies. The development of tools that enable the deconvolution of immunopeptidomes in the context of disease can help improve the specificity and effectiveness of therapeutic strategies targeting these peptides, such as adoptive T-cell therapy and vaccines. Here, we describe a computational workflow that facilitates the processing and interpretation of data-independent acquisition mass spectrometry (DIA-MS). We consider a specific variation of DIA-MS known as SWATH-MS. SWATH-MS is a promising technique that can be utilized to reproducibly characterize and quantify immunopeptidomes isolated from a wide range of biological sources. In this workflow, we use an assortment of database search engines and computational tools to build high-quality HLA allele-specific peptide spectral peptide libraries for the analysis of immunopeptidomic datasets acquired by SWATH-MS. Generating and sharing these spectral libraries are essential for the SWATH-MS technology to meet its full potential and to enable the rapid and reproducible quantification of HLA-specific peptides across multiple samples.
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Affiliation(s)
- Kevin Kovalchik
- CHU Sainte-Justine Research Center, Montreal, QC H3T 1C5, Canada.
| | - David Hamelin
- CHU Sainte-Justine Research Center, Montreal, QC H3T 1C5, Canada
| | - Etienne Caron
- CHU Sainte-Justine Research Center, Montreal, QC H3T 1C5, Canada. .,Department of Pathology and Cellular Biology, Faculty of Medicine, Université de Montréal, Montreal, QC H3T 1J4, Canada.
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43
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Aevermann BD, Shannon CP, Novotny M, Ben-Othman R, Cai B, Zhang Y, Ye JC, Kobor MS, Gladish N, Lee AHY, Blimkie TM, Hancock RE, Llibre A, Duffy D, Koff WC, Sadarangani M, Tebbutt SJ, Kollmann TR, Scheuermann RH. Machine Learning-Based Single Cell and Integrative Analysis Reveals That Baseline mDC Predisposition Correlates With Hepatitis B Vaccine Antibody Response. Front Immunol 2021; 12:690470. [PMID: 34777332 PMCID: PMC8588842 DOI: 10.3389/fimmu.2021.690470] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Accepted: 08/25/2021] [Indexed: 01/23/2023] Open
Abstract
Vaccination to prevent infectious disease is one of the most successful public health interventions ever developed. And yet, variability in individual vaccine effectiveness suggests that a better mechanistic understanding of vaccine-induced immune responses could improve vaccine design and efficacy. We have previously shown that protective antibody levels could be elicited in a subset of recipients with only a single dose of the hepatitis B virus (HBV) vaccine and that a wide range of antibody levels were elicited after three doses. The immune mechanisms responsible for this vaccine response variability is unclear. Using single cell RNA sequencing of sorted innate immune cell subsets, we identified two distinct myeloid dendritic cell subsets (NDRG1-expressing mDC2 and CDKN1C-expressing mDC4), the ratio of which at baseline (pre-vaccination) correlated with the immune response to a single dose of HBV vaccine. Our results suggest that the participants in our vaccine study were in one of two different dendritic cell dispositional states at baseline – an NDRG2-mDC2 state in which the vaccine elicited an antibody response after a single immunization or a CDKN1C-mDC4 state in which the vaccine required two or three doses for induction of antibody responses. To explore this correlation further, genes expressed in these mDC subsets were used for feature selection prior to the construction of predictive models using supervised canonical correlation machine learning. The resulting models showed an improved correlation with serum antibody titers in response to full vaccination. Taken together, these results suggest that the propensity of circulating dendritic cells toward either activation or suppression, their “dispositional endotype” at pre-vaccination baseline, could dictate response to vaccination.
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Affiliation(s)
- Brian D Aevermann
- Department of Informatics, J. Craig Venter Institute, La Jolla, CA, United States
| | - Casey P Shannon
- Prevention of Organ Failure (PROOF) Centre of Excellence, St. Paul's Hospital, Vancouver, BC, Canada.,The University of British Columbia (UBC) Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, BC, Canada
| | - Mark Novotny
- Department of Informatics, J. Craig Venter Institute, La Jolla, CA, United States
| | - Rym Ben-Othman
- Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada.,Telethon Kids Institute, Perth Children's Hospital, University of Western Australia, Nedlands, WA, Australia
| | - Bing Cai
- Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada
| | - Yun Zhang
- Department of Informatics, J. Craig Venter Institute, La Jolla, CA, United States
| | - Jamie C Ye
- Prevention of Organ Failure (PROOF) Centre of Excellence, St. Paul's Hospital, Vancouver, BC, Canada.,The University of British Columbia (UBC) Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, BC, Canada
| | - Michael S Kobor
- Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada
| | - Nicole Gladish
- Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada
| | - Amy Huei-Yi Lee
- Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada
| | - Travis M Blimkie
- Department of Microbiology and Immunology, Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada
| | - Robert E Hancock
- Department of Microbiology and Immunology, Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada
| | - Alba Llibre
- Translational Immunology Lab, Institut Pasteur, Paris, France
| | - Darragh Duffy
- Translational Immunology Lab, Institut Pasteur, Paris, France
| | - Wayne C Koff
- Human Vaccines Project, New York, NY, United States
| | - Manish Sadarangani
- Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada.,Vaccine Evaluation Center, BC Children's Hospital Research Institute, Vancouver, BC, Canada
| | - Scott J Tebbutt
- Prevention of Organ Failure (PROOF) Centre of Excellence, St. Paul's Hospital, Vancouver, BC, Canada.,The University of British Columbia (UBC) Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, BC, Canada.,Department of Medicine, Division of Respiratory Medicine, University of British Columbia, Vancouver, BC, Canada
| | - Tobias R Kollmann
- Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada.,Telethon Kids Institute, Perth Children's Hospital, University of Western Australia, Nedlands, WA, Australia
| | - Richard H Scheuermann
- Department of Informatics, J. Craig Venter Institute, La Jolla, CA, United States.,Department of Pathology, University of California, San Diego, San Diego, CA, United States.,Division of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA, United States
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44
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Fiege JK, Block KE, Pierson MJ, Nanda H, Shepherd FK, Mickelson CK, Stolley JM, Matchett WE, Wijeyesinghe S, Meyerholz DK, Vezys V, Shen SS, Hamilton SE, Masopust D, Langlois RA. Mice with diverse microbial exposure histories as a model for preclinical vaccine testing. Cell Host Microbe 2021; 29:1815-1827.e6. [PMID: 34731647 DOI: 10.1016/j.chom.2021.10.001] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2021] [Revised: 08/30/2021] [Accepted: 10/08/2021] [Indexed: 12/13/2022]
Abstract
Laboratory mice comprise an expeditious model for preclinical vaccine testing; however, vaccine immunogenicity in these models often inadequately translates to humans. Reconstituting physiologic microbial experience to specific pathogen-free (SPF) mice induces durable immunological changes that better recapitulate human immunity. We examined whether mice with diverse microbial experience better model human responses post vaccination. We co-housed laboratory mice with pet-store mice, which have varied microbial exposures, and then assessed immune responses to influenza vaccines. Human transcriptional responses to influenza vaccination are better recapitulated in co-housed mice. Although SPF and co-housed mice were comparably susceptible to acute influenza infection, vaccine-induced humoral responses were dampened in co-housed mice, resulting in poor control upon challenge. Additionally, protective heterosubtypic T cell immunity was compromised in co-housed mice. Because SPF mice exaggerated humoral and T cell protection upon influenza vaccination, reconstituting microbial experience in laboratory mice through co-housing may better inform preclinical vaccine testing.
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Affiliation(s)
- Jessica K Fiege
- Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55455, USA; Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA
| | - Katharine E Block
- Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA
| | - Mark J Pierson
- Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA
| | - Hezkiel Nanda
- Institute for Health Informatics, University of Minnesota, Minneapolis, MN 55455, USA
| | - Frances K Shepherd
- Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55455, USA; Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA
| | - Clayton K Mickelson
- Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55455, USA; Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA
| | - J Michael Stolley
- Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55455, USA; Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA
| | - William E Matchett
- Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55455, USA; Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA
| | - Sathi Wijeyesinghe
- Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55455, USA; Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA
| | - David K Meyerholz
- Department of Pathology, University of Iowa, Iowa City, IA 52242, USA
| | - Vaiva Vezys
- Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55455, USA; Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA
| | - Steven S Shen
- Institute for Health Informatics, University of Minnesota, Minneapolis, MN 55455, USA
| | - Sara E Hamilton
- Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA.
| | - David Masopust
- Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55455, USA; Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA.
| | - Ryan A Langlois
- Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55455, USA; Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA.
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Abstract
Elicitation of lung tissue-resident memory CD8 T cells (TRMs) is a goal of T cell-based vaccines against respiratory viral pathogens, such as influenza A virus (IAV). C-C chemokine receptor type 2 (CCR2)-dependent monocyte trafficking plays an essential role in the establishment of CD8 TRMs in lungs of IAV-infected mice. Here, we used a combination adjuvant-based subunit vaccine strategy that evokes multifaceted (TC1/TC17/TH1/TH17) IAV nucleoprotein-specific lung TRMs to determine whether CCR2 and monocyte infiltration are essential for vaccine-induced TRM development and protective immunity to IAV in lungs. Following intranasal vaccination, neutrophils, monocytes, conventional dendritic cells (DCs), and monocyte-derived dendritic cells internalized and processed vaccine antigen in lungs. We found that basic leucine zipper ATF-like transcription factor 3 (BATF3)-dependent DCs were essential for eliciting T cell responses, but CCR2 deficiency enhanced the differentiation of CD127hi, KLRG-1lo, OX40+ve CD62L+ve, and mucosally imprinted CD69+ve CD103+ve effector and memory CD8 T cells in lungs and airways of vaccinated mice. Mechanistically, increased development of lung TRMs induced by CCR2 deficiency was linked to dampened expression of T-bet but not altered TCF-1 levels or T cell receptor signaling in CD8 T cells. T1/T17 functional programming, parenchymal localization of CD8/CD4 effector and memory T cells, recall T cell responses, and protective immunity to a lethal IAV infection were unaffected in CCR2-deficient mice. Taken together, we identified a negative regulatory role for CCR2 and monocyte trafficking in mucosal imprinting and differentiation of vaccine-induced TRMs. Mechanistic insights from this study may aid the development of T-cell-based vaccines against respiratory viral pathogens, including IAV and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). IMPORTANCE While antibody-based immunity to influenza A virus (IAV) is type and subtype specific, lung- and airway-resident memory T cells that recognize conserved epitopes in the internal viral proteins are known to provide heterosubtypic immunity. Hence, broadly protective IAV vaccines need to elicit robust T cell memory in the respiratory tract. We have developed a combination adjuvant-based IAV nucleoprotein vaccine that elicits strong CD4 and CD8 T cell memory in lungs and protects against H1N1 and H5N1 strains of IAV. In this study, we examined the mechanisms that control vaccine-induced protective memory T cells in the respiratory tract. We found that trafficking of monocytes into lungs might limit the development of antiviral lung-resident memory T cells following intranasal vaccination. These findings suggest that strategies that limit monocyte infiltration can potentiate vaccine-induced frontline T-cell immunity to respiratory viruses, such as IAV and SARS-CoV-2.
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46
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Gamba JC, Roldán C, Prochetto E, Lupi G, Bontempi I, Poncini CV, Vermeulen M, Pérez AR, Marcipar I, Cabrera G. Targeting Myeloid-Derived Suppressor Cells to Enhance a Trans-Sialidase-Based Vaccine Against Trypanosoma cruzi. Front Cell Infect Microbiol 2021; 11:671104. [PMID: 34295832 PMCID: PMC8290872 DOI: 10.3389/fcimb.2021.671104] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Accepted: 06/14/2021] [Indexed: 12/16/2022] Open
Abstract
Trypanosoma cruzi (T. cruzi) is a hemoflagellate protozoan parasite that causes Chagas disease, a neglected tropical disease that affects more than 6 million people around the world, mostly in Latin America. Despite intensive research, there is no vaccine available; therefore, new approaches are needed to further improve vaccine efficacy. It is well established that experimental T. cruzi infection induces a marked immunosuppressed state, which includes notably increases of CD11b+ GR-1+ myeloid-derived suppressor cells (MDSCs) in the spleen, liver and heart of infected mice. We previously showed that a trans-sialidase based vaccine (TSf-ISPA) is able to confer protection against a virulent T. cruzi strain, stimulating the effector immune response and decreasing CD11b+ GR-1+ splenocytes significantly. Here, we show that even in the immunological context elicited by the TSf-ISPA vaccine, the remaining MDSCs are still able to influence several immune populations. Depletion of MDSCs with 5 fluorouracil (5FU) at day 15 post-infection notably reshaped the immune response, as evidenced by flow cytometry of spleen cells obtained from mice after 21 days post-infection. After infection, TSf-ISPA-vaccinated and 5FU-treated mice showed a marked increase of the CD8 response, which included an increased expression of CD107a and CD44 markers in CD8+ cultured splenocytes. In addition, vaccinated and MDSC depleted mice showed an increase in the percentage and number of CD4+ Foxp3+ regulatory T cells (Tregs) as well as in the expression of Foxp3+ in CD4+ splenocytes. Furthermore, depletion of MDSCs also caused changes in the percentage and number of CD11chigh CD8α+ dendritic cells as well as in activation/maturation markers such as CD80, CD40 and MHCII. Thus, the obtained results suggest that MDSCs not only play a role suppressing the effector response during T. cruzi infection, but also strongly modulate the immune response in vaccinated mice, even when the vaccine formulation has a significant protective capacity. Although MDSC depletion at day 15 post-infection did not ameliorated survival or parasitemia levels, depletion of MDSCs during the first week of infection caused a beneficial trend in parasitemia and mice survival of vaccinated mice, supporting the possibility to target MDSCs from different approaches to enhance vaccine efficacy. Finally, since we previously showed that TSf-ISPA immunization causes a slight but significant increase of CD11b+ GR-1+ splenocytes, here we also targeted those cells at the stage of immunization, prior to T. cruzi challenge. Notably, 5FU administration before each dose of TSf-ISPA vaccine was able to significantly ameliorate survival and decrease parasitemia levels of TSf-ISPA-vaccinated and infected mice. Overall, this work supports that targeting MDSCs may be a valuable tool during vaccine design against T. cruzi, and likely for other pathologies that are characterized by the subversion of the immune system.
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Affiliation(s)
- Juan Cruz Gamba
- Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina
| | - Carolina Roldán
- Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina
| | - Estefanía Prochetto
- Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina
| | - Giuliana Lupi
- Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina
| | - Iván Bontempi
- Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina.,Facultad de Ciencias Médicas, Universidad Nacional del Litoral, Santa Fe, Argentina
| | - Carolina Verónica Poncini
- Departamento de Microbiología, Parasitología e Inmunología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina
| | - Mónica Vermeulen
- Laboratorio de Inmunología Oncológica, Instituto de Medicina Experimental (IMEX-CONICET), Academia Nacional de Medicina, Buenos Aires, Argentina
| | - Ana Rosa Pérez
- IDICER-CONICET and Instituto de Inmunología, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Santa Fe, Argentina
| | - Iván Marcipar
- Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina.,Facultad de Ciencias Médicas, Universidad Nacional del Litoral, Santa Fe, Argentina
| | - Gabriel Cabrera
- Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina.,Facultad de Ciencias Médicas, Universidad Nacional del Litoral, Santa Fe, Argentina
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Shah NJ, Aloysius MM, Sharma NR, Pallav K. Advances in treatment and prevention of hepatitis B. World J Gastrointest Pharmacol Ther 2021. [DOI: 10.4292/wjg.v12.i4.56] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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Shah NJ, Aloysius MM, Sharma NR, Pallav K. Advances in treatment and prevention of hepatitis B. World J Gastrointest Pharmacol Ther 2021; 12:56-78. [PMID: 34316384 PMCID: PMC8290928 DOI: 10.4292/wjgpt.v12.i4.56] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Revised: 03/22/2021] [Accepted: 05/22/2021] [Indexed: 02/06/2023] Open
Abstract
Chronic hepatitis B (CHB) continues to contribute to worldwide morbidity and mortality significantly. Scientists, clinicians, pharmaceutical companies, and health organizations have dedicated substantial Intellectual and monetary resources to finding a cure, increasing immunization rates, and reducing the global burden of CHB. National and international health-related organizations including the center for disease control, the national institute of health, the American Association for the study of liver disease (AASLD), The European association for the study of the Liver (EASL), The Asia Pacific association for the study of the Liver (APASL) and the world health organization release periodic recommendations for disease prevention and treatment. Our review of the most recent guidelines by EASL, AASLD, APASL, and Taiwan Association for the Study of the Liver revealed that an overwhelming majority of cited studies were published before 2018. We reviewed Hepatitis B-related literature published 2018 onwards to identify recent developments and current barriers that will likely direct future efforts towards eradicating hepatitis B. The breakthrough in our understanding of the hepatitis B virus life cycle and resulting drug development is encouraging with significant room for further progress. Data from high-risk populations, most vulnerable to the devastating effects of hepatitis B infection and reactivation remain sparse. Utilization of systems approach, optimization of experimental models, identification and validation of next-generation biomarkers, and precise modulation of the human immune response will be critical for future innovation. Within the foreseeable future, new treatments will likely complement conventional therapies rather than replace them. Most Importantly, pragmatic management of CHB related population health challenges must be prioritized to produce real-world results.
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Affiliation(s)
- Niraj James Shah
- Department of Internal Medicine, Digestive Disease, University of Mississippi Medical Center, Jackson, MS 39216, United States
| | - Mark M Aloysius
- Department of Internal Medicine, The Wright Center for Graduate Medical Education, Scranton, PA 18505, United States
| | - Neil Rohit Sharma
- Department of Internal Medicine, Interventional Oncology and Surgical Endoscopy, Parkview Regional Medical Center, Parkview Cancer Institute, Fort Wayne, IN 46845, United States
| | - Kumar Pallav
- Department of Internal Medicine, Interventional Oncology and Surgical Endoscopy, Parkview Regional Medical Center, Parkview Cancer Institute, Fort Wayne, IN 46845, United States
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Vandergaast R, Carey T, Reiter S, Lathrum C, Lech P, Gnanadurai C, Haselton M, Buehler J, Narjari R, Schnebeck L, Roesler A, Sevola K, Suksanpaisan L, Bexon A, Naik S, Brunton B, Weaver SC, Rafael G, Tran S, Baum A, Kyratsous CA, Peng KW, Russell SJ. IMMUNO-COV v2.0: Development and Validation of a High-Throughput Clinical Assay for Measuring SARS-CoV-2-Neutralizing Antibody Titers. mSphere 2021; 6:e0017021. [PMID: 34077262 PMCID: PMC8265629 DOI: 10.1128/msphere.00170-21] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Accepted: 05/18/2021] [Indexed: 01/22/2023] Open
Abstract
Neutralizing antibodies are key determinants of protection from future infection, yet well-validated high-throughput assays for measuring titers of SARS-CoV-2-neutralizing antibodies are not generally available. Here, we describe the development and validation of IMMUNO-COV v2.0, a scalable surrogate virus assay, which titrates antibodies that block infection of Vero-ACE2 cells by a luciferase-encoding vesicular stomatitis virus displaying SARS-CoV-2 spike glycoproteins (VSV-SARS2-Fluc). Antibody titers, calculated using a standard curve consisting of stepped concentrations of SARS-CoV-2 spike monoclonal antibody, correlated closely (P < 0.0001) with titers obtained from a gold standard 50% plaque-reduction neutralization test (PRNT50%) performed using a clinical isolate of SARS-CoV-2. IMMUNO-COV v2.0 was comprehensively validated using data acquired from 242 assay runs performed over 7 days by five analysts, utilizing two separate virus lots, and 176 blood samples. Assay performance was acceptable for clinical use in human serum and plasma based on parameters including linearity, dynamic range, limit of blank and limit of detection, dilutional linearity and parallelism, precision, clinical agreement, matrix equivalence, clinical specificity and sensitivity, and robustness. Sufficient VSV-SARS2-Fluc virus reagent has been banked to test 5 million clinical samples. Notably, a significant drop in IMMUNO-COV v2.0 neutralizing antibody titers was observed over a 6-month period in people recovered from SARS-CoV-2 infection. Together, our results demonstrate the feasibility and utility of IMMUNO-COV v2.0 for measuring SARS-CoV-2-neutralizing antibodies in vaccinated individuals and those recovering from natural infections. Such monitoring can be used to better understand what levels of neutralizing antibodies are required for protection from SARS-CoV-2 and what booster dosing schedules are needed to sustain vaccine-induced immunity. IMPORTANCE Since its emergence at the end of 2019, SARS-CoV-2, the causative agent of COVID-19, has caused over 100 million infections and 2.4 million deaths worldwide. Recently, countries have begun administering approved COVID-19 vaccines, which elicit strong immune responses and prevent disease in most vaccinated individuals. A key component of the protective immune response is the production of neutralizing antibodies capable of preventing future SARS-CoV-2 infection. Yet, fundamental questions remain regarding the longevity of neutralizing antibody responses following infection or vaccination and the level of neutralizing antibodies required to confer protection. Our work is significant as it describes the development and validation of a scalable clinical assay that measures SARS-CoV-2-neutraling antibody titers. We have critical virus reagent to test over 5 million samples, making our assay well suited for widespread monitoring of SARS-CoV-2-neutralizing antibodies, which can in turn be used to inform vaccine dosing schedules and answer fundamental questions regarding SARS-CoV-2 immunity.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | - Kara Sevola
- Imanis Life Sciences, Rochester, Minnesota, USA
| | | | | | - Shruthi Naik
- Vyriad, Inc., Rochester, Minnesota, USA
- Mayo Clinic Department of Molecular Medicine, Rochester, Minnesota, USA
| | | | - Scott C. Weaver
- World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, Texas, USA
- Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, Texas, USA
- Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA
| | - Grace Rafael
- World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, Texas, USA
- Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, Texas, USA
- Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA
| | | | - Alina Baum
- Regeneron Pharmaceuticals Inc., Tarrytown, New York, USA
| | | | - Kah Whye Peng
- Imanis Life Sciences, Rochester, Minnesota, USA
- Vyriad, Inc., Rochester, Minnesota, USA
- Mayo Clinic Department of Molecular Medicine, Rochester, Minnesota, USA
| | - Stephen J. Russell
- Imanis Life Sciences, Rochester, Minnesota, USA
- Vyriad, Inc., Rochester, Minnesota, USA
- Mayo Clinic Department of Molecular Medicine, Rochester, Minnesota, USA
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Combination Adjuvants Affect the Magnitude of Effector-Like Memory CD8 T Cells and Protection against Listeriosis. Infect Immun 2021; 89:e0076820. [PMID: 33782151 DOI: 10.1128/iai.00768-20] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
The development of T cell-based subunit protein vaccines against diseases such as tuberculosis and malaria remains a challenge for immunologists. Here, we have identified a nanoemulsion adjuvant, Adjuplex (ADJ), which enhanced dendritic cell (DC) cross-presentation and elicited effective memory T cell-based immunity to Listeria monocytogenes. We further evaluated whether cross-presentation induced by ADJ can be combined with the immunomodulatory effects of Toll-like receptor (TLR) agonists (CpG or glucopyranosyl lipid adjuvant [GLA]) to evoke systemic CD8 T cell-based immunity to L. monocytogenes. Mechanistically, vaccination with ADJ, alone or in combination with CpG or GLA, augmented activation and antigen uptake by CD103+ migratory and CD8α+ resident DCs and upregulated CD69 expression on B and T lymphocytes in vaccine-draining lymph nodes. By engaging basic leucine zipper ATF-like transcription factor 3-dependent cross-presenting DCs, ADJ potently elicited effector CD8 T cells that differentiated into granzyme B-expressing CD27LO effector-like memory CD8 T cells, which provided effective immunity to L. monocytogenes in the spleen and liver. CpG or GLA alone did not elicit effector-like memory CD8 T cells and induced moderate protection in the spleen but not in the liver. Surprisingly, combining CpG or GLA with ADJ reduced the number of ADJ-induced memory CD8 T cells and compromised protective immunity to L. monocytogenes, especially in the liver. Taken together, the data presented in this study provide a glimpse of protective CD8 T cell memory differentiation induced by a nanoemulsion adjuvant and demonstrate the unexpected negative effects of TLR signaling on the magnitude of CD8 T cell memory and protective immunity to L. monocytogenes, a model intracellular pathogen.
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