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Mohammadi K, Faramarzi S, Yaribash S, Valizadeh Z, Rajabi E, Ghavam M, Samiee R, Karim B, Salehi M, Seifi A, Shafaati M. Human metapneumovirus (hMPV) in 2025: emerging trends and insights from community and hospital-based respiratory panel analyses-a comprehensive review. Virol J 2025; 22:150. [PMID: 40394641 PMCID: PMC12090560 DOI: 10.1186/s12985-025-02782-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2025] [Accepted: 05/08/2025] [Indexed: 05/22/2025] Open
Abstract
Human metapneumovirus (hMPV) is a significant respiratory pathogen, primarily impacting young, elderly, and immunocompromised populations. While the clinical presentations are similar to those of other respiratory viruses such as respiratory syncytial virus (RSV), influenza, and SARS-CoV-2, they can still lead to serious complications. The virus primarily transmits via respiratory droplets, with outbreaks peaking during winter and spring. In resource-limited settings, administration of multiplex PCR assays is essential for precise diagnosis, yet it presents significant challenges. Recent studies indicate a 6.24% infection rate in hospitalized patients presenting with acute respiratory infections (ARIs). Enhanced surveillance and prevention are essential given the morbidity and mortality rates of hMPV, which are comparable to those of influenza and RSV. Effective management requires enhanced diagnostic tools, improved public health strategies, and continuous research into antiviral therapies and vaccines. This study highlighted the growing importance of hMPV as a respiratory pathogen, focusing on its seasonal patterns, clinical manifestations in at-risk populations, transmission dynamics, and diagnostic challenges compared to other respiratory viruses.
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Affiliation(s)
- Keyhan Mohammadi
- Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
- Research Center for Antibiotic Stewardship and Antimicrobial Resistance, Infectious Diseases Department, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Samireh Faramarzi
- Razi Vaccine and Serum Research Institute, Agricultural Research Education and Extension Organization, Karaj, Iran
| | - Shakila Yaribash
- Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Zahra Valizadeh
- Iranian Research Center for HIV/AIDS, Iranian Institute for Reduction of High-Risk Behaviors, Tehran University of Medical Sciences, Tehran, Iran
| | - Erta Rajabi
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Ghavam
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Reza Samiee
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Bardia Karim
- Department of Pharmacology and Toxicology, School of Medicine, Babol University of Medical Sciences, Babol, Iran
| | - Mohammadreza Salehi
- Research Center for Antibiotic Stewardship and Antimicrobial Resistance, Infectious Diseases Department, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Arash Seifi
- Research Center for Antibiotic Stewardship and Antimicrobial Resistance, Infectious Diseases Department, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
- Center for Communicable Disease Control, IPC/AMR Office, Ministry of Health and Medical Education, Tehran, Iran
| | - Maryam Shafaati
- Research Center for Antibiotic Stewardship and Antimicrobial Resistance, Infectious Diseases Department, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran.
- Center for Communicable Disease Control, IPC/AMR Office, Ministry of Health and Medical Education, Tehran, Iran.
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Kim SJ, Kim HJ, Noh YH, Won HK, Hong SM, Yoon IJ, Choi KS. Preclinical evaluation of a live avian metapneumovirus subtype B vaccine strain with cross-protective efficacy in chickens. Poult Sci 2025; 104:105283. [PMID: 40398299 DOI: 10.1016/j.psj.2025.105283] [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: 03/14/2025] [Revised: 05/08/2025] [Accepted: 05/09/2025] [Indexed: 05/23/2025] Open
Abstract
Avian metapneumovirus (aMPV) infection is an important respiratory disease that causes significant economic loss in the poultry industry. Here, we aimed to develop an effective live aMPV subtype B vaccine strain suitable for mass vaccination of poultry farms to achieve herd immunity. The wild-type virus was attenuated by serial passaging in Vero-K cells, and the genetic stability of the attenuated virus was evaluated through genomic sequencing analysis. The attenuated virus was formulated into test pilot live vaccines. Preclinical tests of the test vaccine, including those measuring indices of safety, minimum immunogenicity, virulence reversion, immunogenicity and cross-protective efficacy, were conducted in SPF chickens. The master seed virus (MSV) of the SNU21004(a) vaccine strain was established by serial passaging in Vero-K cells. Some point mutations occurred throughout the viral genome, but no gene deletions or insertions were observed. The clinical scores, histopathological scores, and viral loads of SPF chickens inoculated with the MSV were significantly lower than those inoculated with the wild-type virus (P < 0.05). There was no increase in viral virulence after five backpassages in chickens. The minimal immunogenicity dose for protection against aMPV is 102.1 TCID50/dose. The test vaccine induced a strong humoral immune response and efficiently protected chickens, even in vaccinated birds with low antibody titers, regardless of the route of administration (drinking water or spraying) or challenge virus subtype (subtypes A and B). The SNU21004(a) vaccine strain was found to be safe and highly immunogenic even at small doses in chickens and showed cross-protection against other aMPV infections.
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Affiliation(s)
- Sae-Jin Kim
- Laboratory of Avian Diseases, Research Institute for Veterinary Science and College of Veterinary Medicine for Veterinary Science, Seoul National University, Seoul 088026, Republic of Korea; Choong Ang Vaccine Laboratories Co., Ltd. (CAVAC), Daejeon 34055, Republic of Korea
| | - Hyun-Jin Kim
- Choong Ang Vaccine Laboratories Co., Ltd. (CAVAC), Daejeon 34055, Republic of Korea
| | - Yun-Hee Noh
- Choong Ang Vaccine Laboratories Co., Ltd. (CAVAC), Daejeon 34055, Republic of Korea
| | - Ho-Keun Won
- Choong Ang Vaccine Laboratories Co., Ltd. (CAVAC), Daejeon 34055, Republic of Korea
| | - Seung-Min Hong
- Laboratory of Avian Diseases, Research Institute for Veterinary Science and College of Veterinary Medicine for Veterinary Science, Seoul National University, Seoul 088026, Republic of Korea
| | - In-Joong Yoon
- Choong Ang Vaccine Laboratories Co., Ltd. (CAVAC), Daejeon 34055, Republic of Korea
| | - Kang-Seuk Choi
- Laboratory of Avian Diseases, Research Institute for Veterinary Science and College of Veterinary Medicine for Veterinary Science, Seoul National University, Seoul 088026, Republic of Korea.
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Marchand GJ, Massoud AT, Abdelsattar AT, McCullough PA. RSVpreF vaccination in pregnancy: a meta-analysis of maternal-fetal safety and infant efficacy. Obstet Gynecol Sci 2024; 67:511-524. [PMID: 39327769 PMCID: PMC11581813 DOI: 10.5468/ogs.24213] [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: 08/04/2024] [Revised: 09/07/2024] [Accepted: 09/10/2024] [Indexed: 09/28/2024] Open
Abstract
In May 2023, the United States Food and Drug Administration approved a Pfizer©-sponsored (Pfizer, New York, NY, USA) bivalent respiratory syncytial virus prefusion F protein-based vaccine (RSVpreF) RSV vaccine (AbrysvoTM [Pfizer]) for use during pregnancy to prevent neonatal/infant RSV infection. In February of 2022, trials sponsored by GSK© (Brentford, England, UK) on a similar RSVpreF vaccine were halted because of the identification of a safety signal related to preterm births. As these vaccines use identical pre-fusion F-protein technology, we sought to synthesize the existing data on their effectiveness and safety. We identified all randomized controlled trials and used RevMan 5.4.1 (The Cochrane Collaboration, England, UK) to perform the analysis with 95% confidence intervals and risk ratios (RRs). We found many maternal side effects were more prevalent in the RSVpreF group, with more local reactions, blood disorders, fatigue, joint pain, cardiac disorders, headache, fever, gastrointestinal disorders and pregnancy complications. The vaccinated group demonstrated significant reductions in RSV-lower respiratory tract cases (RR, 0.44 [0.33, 0.57]; P<0.00001), severe respiratory illness (RR, 0.29 [0.19, 0.44]; P<0.00001), and hospitalizations (RR, 0.40 [0.24, 0.67]; P=0.0005). RSVpreF vaccination was associated with a higher incidence of preterm delivery (RR, 1.24 [1.08, 1.44]; P=0.003). No significant difference in neonatal deaths was observed (RR, 1.42 [0.70, 2.89]; P=0.34). In conclusion, RSVpreF vaccination results in systemic adverse events and an increase in preterm delivery. Vaccination appears to have acceptable short-term newborn safety, but is not related to a significant decrease in neonatal death.
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Affiliation(s)
- Greg J. Marchand
- Department of Research, Marchand Institute for Minimally Invasive Surgery, Mesa, AZ, USA
| | - Ahmed Taher Massoud
- Department of Research, Marchand Institute for Minimally Invasive Surgery, Mesa, AZ, USA
- Department of Medicine, Fayoum University Faculty of Medicine, Fayoum, Egypt
| | - Ahmed Taha Abdelsattar
- Department of Research, Marchand Institute for Minimally Invasive Surgery, Mesa, AZ, USA
- Department of Medicine, Fayoum University Faculty of Medicine, Fayoum, Egypt
| | - Peter A. McCullough
- Department of Internal Medicine, Cardiology, McCullough Foundation, Dallas Texas, TX, USA
- Department of Internal Medicine, Cardiology, Truth for Health Foundation, Tucson, AZ, USA
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Lin ZL, Xu X, Yang JJ, Lu LQ, Huang H, Hua XZ, Lu LD. Efficacy of budesonide/formoterol inhalation powder in treating viral pneumonia in children. World J Clin Cases 2024; 12:4469-4475. [PMID: 39070822 PMCID: PMC11235498 DOI: 10.12998/wjcc.v12.i21.4469] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2024] [Revised: 05/09/2024] [Accepted: 05/21/2024] [Indexed: 06/30/2024] Open
Abstract
BACKGROUND Respiratory viruses are increasingly detected in children with community-acquired pneumonia. Further strategies to limit antibiotic use in children with viral pneumonia are warranted. AIM To explore clinical efficacy of budesonide/formoterol inhalation powder for viral pneumonia in children and its impact on cellular immunity and inflammatory factor production. METHODS A total of 60 children with viral pneumonia were recruited: 30 receiving budesonide/formoterol inhalation powder and 30 conventional symptomatic treatment. Outcome measures included peripheral blood levels of inflammatory cytokines, CD4+, CD8+, Th1, Th2, Th17 and Treg, clinical efficacy, and incidence of adverse reactions. RESULTS Compared with the control group, the observation group showed a significant reduction in interleukin-6 and high-sensitivity C-reactive protein levels after treatment. Compared with the control group, the observation group showed a significant increase in CD4+/CD8+ and Th1/Th2 levels, and a decrease in Th17/Treg levels after treatment. The total effective rates in the observation group and the control group were 93.75% and 85.00%, respectively, which was a significant difference (P = 0.003). CONCLUSION Budesonide/formoterol inhalation powder significantly improved therapeutic efficacy for viral pneumonia in children. The mechanism of action may be related to downregulation of the inflammatory response and improved cellular immune function.
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Affiliation(s)
- Zi-Liang Lin
- Department of Pediatrics, Cangnan Hospital Affiliated to Wenzhou Medical University, Wenzhou 325800, Zhejiang Province, China
| | - Xu Xu
- Department of Pediatrics, Cangnan Hospital Affiliated to Wenzhou Medical University, Wenzhou 325800, Zhejiang Province, China
| | - Jiao-Jiao Yang
- Department of Pediatrics, Cangnan Hospital Affiliated to Wenzhou Medical University, Wenzhou 325800, Zhejiang Province, China
| | - Li-Qiang Lu
- Department of Pediatrics, Cangnan Hospital Affiliated to Wenzhou Medical University, Wenzhou 325800, Zhejiang Province, China
| | - Heng Huang
- Department of Pediatrics, Cangnan Hospital Affiliated to Wenzhou Medical University, Wenzhou 325800, Zhejiang Province, China
| | - Xiao-Zhen Hua
- Department of Pediatrics, Cangnan Hospital Affiliated to Wenzhou Medical University, Wenzhou 325800, Zhejiang Province, China
| | - Li-Dang Lu
- Department of Pediatrics, Cangnan Hospital Affiliated to Wenzhou Medical University, Wenzhou 325800, Zhejiang Province, China
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Chang LA, Schotsaert M. Ally, adversary, or arbitrator? The context-dependent role of eosinophils in vaccination for respiratory viruses and subsequent breakthrough infections. J Leukoc Biol 2024; 116:224-243. [PMID: 38289826 PMCID: PMC11288382 DOI: 10.1093/jleuko/qiae010] [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: 10/29/2023] [Revised: 12/12/2023] [Accepted: 12/26/2023] [Indexed: 02/01/2024] Open
Abstract
Eosinophils are a critical type of immune cell and central players in type 2 immunity. Existing literature suggests that eosinophils also can play a role in host antiviral responses, typically type 1 immune events, against multiple respiratory viruses, both directly through release of antiviral mediators and indirectly through activation of other effector cell types. One way to prime host immune responses toward effective antiviral responses is through vaccination, where typically a type 1-skewed immunity is desirable in the context of intracellular pathogens like respiratory viruses. In the realm of breakthrough respiratory viral infection in vaccinated hosts, an event in which virus can still establish productive infection despite preexisting immunity, eosinophils are most prominently known for their link to vaccine-associated enhanced respiratory disease upon natural respiratory syncytial virus infection. This was observed in a pediatric cohort during the 1960s following vaccination with formalin-inactivated respiratory syncytial virus. More recent research has unveiled additional roles of the eosinophil in respiratory viral infection and breakthrough infection. The specific contribution of eosinophils to the quality of vaccine responses, vaccine efficacy, and antiviral responses to infection in vaccinated hosts remains largely unexplored, especially regarding their potential roles in protection. On the basis of current findings, we will speculate upon the suggested function of eosinophils and consider the many potential ways by which eosinophils may exert protective and pathological effects in breakthrough infections. We will also discuss how to balance vaccine efficacy with eosinophil-related risks, as well as the use of eosinophils and their products as potential biomarkers of vaccine efficacy or adverse events.
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Affiliation(s)
- Lauren A Chang
- Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, United States
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1124, New York, NY 10029, United States
- Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1124, New York, NY 10029, United States
| | - Michael Schotsaert
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1124, New York, NY 10029, United States
- Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1124, New York, NY 10029, United States
- Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, Box 1630, New York, NY 10029, United States
- Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, United States
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Flagellin-Fused Protein Targeting M2e and HA2 Induces Innate and T-Cell Responses in Mice of Different Genetic Lines. Vaccines (Basel) 2022; 10:vaccines10122098. [PMID: 36560509 PMCID: PMC9786633 DOI: 10.3390/vaccines10122098] [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: 10/18/2022] [Revised: 11/28/2022] [Accepted: 12/06/2022] [Indexed: 12/13/2022] Open
Abstract
Efficient control of influenza A infection can potentially be achieved through the development of broad-spectrum vaccines. Recombinant proteins incorporating conserved influenza A virus peptides are one of the platforms for the development of cross-protective influenza vaccines. We constructed a recombinant protein Flg-HA2-2-4M2ehs, in which the extracellular domain of the M2 protein (M2e) and the sequence (aa76-130) of the second subunit of HA (HA2) were used as target antigens. In this study, we investigated the ability of the Flg-HA2-2-4M2ehs protein to activate innate immunity and stimulate the formation of T-cell response in mice of different genetic lines after intranasal immunization. Our studies showed that the Flg-HA2-2-4M2ehs protein was manifested in an increase in the relative content of neutrophils, monocytes, and interstitial macrophages, against the backdrop of a decrease in the level of dendritic cells and increased expression in the CD86 marker. In the lungs of BALB/c mice, immunization with the Flg-HA2-2-4M2ehs protein induced the formation of antigen-specific CD4+ and CD8+ effector memory T cells, producing TNF-α. In mice C57Bl/6, the formation of antigen-specific effector CD8+ T cells, predominantly producing IFN-γ+, was demonstrated. The data obtained showed the formation of CD8+ and CD4+ effector memory T cells expressing the CD107a.
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Sabitha S, Shobana N, Prakash P, Padmanaban S, Sathiyashree M, Saigeetha S, Chakravarthi S, Uthaman S, Park IK, Samrot AV. A Review of Different Vaccines and Strategies to Combat COVID-19. Vaccines (Basel) 2022; 10:vaccines10050737. [PMID: 35632493 PMCID: PMC9145217 DOI: 10.3390/vaccines10050737] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Revised: 05/05/2022] [Accepted: 05/05/2022] [Indexed: 01/09/2023] Open
Abstract
In December 2019, an unknown viral infection emerged and quickly spread worldwide, resulting in a global pandemic. This novel virus caused severe pneumonia and acute respiratory distress syndrome caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). It has caused 6.25 millions of deaths worldwide and remains a major concern for health, society, and the economy. As vaccination is one of the most efficient ways to combat this pandemic, different vaccines were developed in a short period. This review article discusses how coronavirus affected the top nations of the world and the vaccines being used for the prevention. Amongst the vaccines, some vaccines have already been approved, and some have been involved in clinical studies. The article also provides insight into different COVID-19 vaccine platforms, their preparation, working, efficacy, and side effects.
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Affiliation(s)
- Srinivasan Sabitha
- School of Bio and Chemical Engineering, Sathyabama Institute of Science and Technology, Sholinganallur, Rajiv Gandhi Salai, Chennai 600119, India; (S.S.); (N.S.); (P.P.); (M.S.)
| | - Nagarajan Shobana
- School of Bio and Chemical Engineering, Sathyabama Institute of Science and Technology, Sholinganallur, Rajiv Gandhi Salai, Chennai 600119, India; (S.S.); (N.S.); (P.P.); (M.S.)
| | - Pandurangan Prakash
- School of Bio and Chemical Engineering, Sathyabama Institute of Science and Technology, Sholinganallur, Rajiv Gandhi Salai, Chennai 600119, India; (S.S.); (N.S.); (P.P.); (M.S.)
| | - Sathiyamoorthy Padmanaban
- Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju 58128, Korea;
- Biomedical Science Graduate Program (BMSGP), Chonnam National University, Gwangju 58128, Korea
| | - Mahendran Sathiyashree
- School of Bio and Chemical Engineering, Sathyabama Institute of Science and Technology, Sholinganallur, Rajiv Gandhi Salai, Chennai 600119, India; (S.S.); (N.S.); (P.P.); (M.S.)
| | - Subramanian Saigeetha
- Department of Biotechnology, School of Biosciences and Technology, Vellore Institute of Technology, Vellore 632014, India;
| | - Srikumar Chakravarthi
- School of Bioscience, Faculty of Medicine, Bioscience and Nursing, MAHSA University, Jalan SP2, Bandar Saujana Putra, Jenjarom 42610, Malaysia;
| | - Saji Uthaman
- Department of Chemical and Biological Engineering, Iowa State University, Ames, IA 50011, USA
- Correspondence: (S.U.); (I.-K.P.); (A.V.S.)
| | - In-Kyu Park
- Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju 58128, Korea;
- Biomedical Science Graduate Program (BMSGP), Chonnam National University, Gwangju 58128, Korea
- Correspondence: (S.U.); (I.-K.P.); (A.V.S.)
| | - Antony V. Samrot
- School of Bioscience, Faculty of Medicine, Bioscience and Nursing, MAHSA University, Jalan SP2, Bandar Saujana Putra, Jenjarom 42610, Malaysia;
- Centre for Materials Engineering and Regenerative Medicine, Bharath Institute of Higher Education and Research, Selaiyur 600073, India
- Correspondence: (S.U.); (I.-K.P.); (A.V.S.)
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Smatti MK, Alkhatib HA, Al Thani AA, Yassine HM. Will Host Genetics Affect the Response to SARS-CoV-2 Vaccines? Historical Precedents. Front Med (Lausanne) 2022; 9:802312. [PMID: 35360730 PMCID: PMC8962369 DOI: 10.3389/fmed.2022.802312] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Accepted: 02/10/2022] [Indexed: 11/25/2022] Open
Abstract
Recent progress in genomics and bioinformatics technologies have allowed for the emergence of immunogenomics field. This intersection of immunology and genetics has broadened our understanding of how the immune system responds to infection and vaccination. While the immunogenetic basis of the huge clinical variability in response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is currently being extensively studied, the host genetic determinants of SARS-CoV-2 vaccines remain largely unknown. Previous reports evidenced that vaccines may not protect all populations or individuals equally, due to multiple host- and vaccine-specific factors. Several studies on vaccine response to measles, rubella, hepatitis B, smallpox, and influenza highlighted the contribution of genetic mutations or polymorphisms in modulating the innate and adaptive immunity following vaccination. Specifically, genetic variants in genes encoding virus receptors, antigen presentation, cytokine production, or related to immune cells activation and differentiation could influence how an individual responds to vaccination. Although such knowledge could be utilized to generate personalized vaccine strategies to optimize the vaccine response, studies in this filed are still scarce. Here, we briefly summarize the scientific literature related to the immunogenetic determinants of vaccine-induced immunity, highlighting the possible role of host genetics in response to SARS-CoV-2 vaccines as well.
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Affiliation(s)
- Maria K. Smatti
- College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar
- Biomedical Research Center, Qatar University, Doha, Qatar
| | | | | | - Hadi M. Yassine
- College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar
- Biomedical Research Center, Qatar University, Doha, Qatar
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9
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Naskalska A, Dabrowska A, Szczepanski A, Jasik KP, Gromadzka B, Pyrc K. Functional Severe Acute Respiratory Syndrome Coronavirus 2 Virus-Like Particles From Insect Cells. Front Microbiol 2021; 12:732998. [PMID: 34745036 PMCID: PMC8565087 DOI: 10.3389/fmicb.2021.732998] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Accepted: 08/30/2021] [Indexed: 12/29/2022] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a major epidemic threat since the beginning of 2020. Efforts to combat the virus and the associated coronavirus disease 2019 (COVID-19) disease are being undertaken worldwide. To facilitate the research on the virus itself, a number of surrogate systems have been developed. Here, we report the efficient production of SARS-CoV-2 virus-like particles (VLPs) in insect cells. Contrary to widely used pseudovirus particles, where only one coronaviral protein is displayed within a heterologous scaffold, developed VLPs are structurally similar to the native virus and allow for more throughput studies on the biology of the infection. On the other hand, being devoid of the viral genome, VLPs are unable to replicate and thus safe to work with. Importantly, this is the first report showing that SARS-CoV-2 VLPs can be efficiently produced in insect cells and purified using scalable affinity chromatography.
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Affiliation(s)
- Antonina Naskalska
- Virogenetics Laboratory of Virology, Malopolska Centre of Biotechnology, Jagiellonian University, Kraków, Poland
| | - Agnieszka Dabrowska
- Virogenetics Laboratory of Virology, Malopolska Centre of Biotechnology, Jagiellonian University, Kraków, Poland.,Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland
| | - Artur Szczepanski
- Virogenetics Laboratory of Virology, Malopolska Centre of Biotechnology, Jagiellonian University, Kraków, Poland.,Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland
| | - Krzysztof P Jasik
- Department of Pathology, School of Pharmacy, Medical University of Silesia in Katowice, Sosnowiec, Poland
| | - Beata Gromadzka
- Department of "in vitro" Studies, Institute of Biotechnology and Molecular Medicine, Gdańsk, Poland.,NanoExpo®, Gdańsk, Poland
| | - Krzysztof Pyrc
- Virogenetics Laboratory of Virology, Malopolska Centre of Biotechnology, Jagiellonian University, Kraków, Poland
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Pogostin BH, McHugh KJ. Novel Vaccine Adjuvants as Key Tools for Improving Pandemic Preparedness. Bioengineering (Basel) 2021; 8:155. [PMID: 34821721 PMCID: PMC8615241 DOI: 10.3390/bioengineering8110155] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Revised: 10/20/2021] [Accepted: 10/22/2021] [Indexed: 02/07/2023] Open
Abstract
Future infectious disease outbreaks are inevitable; therefore, it is critical that we maximize our readiness for these events by preparing effective public health policies and healthcare innovations. Although we do not know the nature of future pathogens, antigen-agnostic platforms have the potential to be broadly useful in the rapid response to an emerging infection-particularly in the case of vaccines. During the current COVID-19 pandemic, recent advances in mRNA engineering have proven paramount in the rapid design and production of effective vaccines. Comparatively, however, the development of new adjuvants capable of enhancing vaccine efficacy has been lagging. Despite massive improvements in our understanding of immunology, fewer than ten adjuvants have been approved for human use in the century since the discovery of the first adjuvant. Modern adjuvants can improve vaccines against future pathogens by reducing cost, improving antigen immunogenicity, and increasing antigen stability. In this perspective, we survey the current state of adjuvant use, highlight potentially impactful preclinical adjuvants, and propose new measures to accelerate adjuvant safety testing and technology sharing to enable the use of "off-the-shelf" adjuvant platforms for rapid vaccine testing and deployment in the face of future pandemics.
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Affiliation(s)
| | - Kevin J. McHugh
- Department of Bioengineering, Rice University, Houston, TX 77030, USA;
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11
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Racine-Brzostek SE, Yee JK, Sukhu A, Qiu Y, Rand S, Barone PD, Hao Y, Yang HS, Meng QH, Apple FS, Shi Y, Chadburn A, Golden E, Formenti SC, Cushing MM, Zhao Z. Rapid, robust, and sustainable antibody responses to mRNA COVID-19 vaccine in convalescent COVID-19 individuals. JCI Insight 2021; 6:e151477. [PMID: 34499052 PMCID: PMC8564891 DOI: 10.1172/jci.insight.151477] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Accepted: 09/08/2021] [Indexed: 12/23/2022] Open
Abstract
Longitudinal studies are needed to evaluate the SARS-CoV-2 mRNA vaccine antibody response under real-world conditions. This longitudinal study investigated the quantity and quality of SARS-CoV-2 antibody response in 846 specimens from 350 patients, comparing BNT162b2-vaccinated individuals (19 previously diagnosed with COVID-19, termed RecoVax; and 49 never diagnosed, termed NaiveVax) with 122 hospitalized unvaccinated (HospNoVax) and 160 outpatient unvaccinated (OutPtNoVax) COVID-19 patients. NaiveVax experienced delay in generating SARS-CoV-2 total antibodies (TAb) and surrogate neutralizing antibodies (SNAb) after the first vaccine dose (D1) but rapid increase in antibody levels after the second dose (D2). However, these never reached RecoVax's robust levels. In fact, NaiveVax TAb and SNAb levels decreased 4 weeks after D2. For the most part, RecoVax TAb persisted, after reaching maximal levels 2 weeks after D2, but SNAb decreased significantly about 6 months after D1. Although NaiveVax avidity lagged behind that of RecoVax for most of the follow-up periods, NaiveVax did reach similar avidity by about 6 months after D1. These data suggest that 1 vaccine dose elicits maximal antibody response in RecoVax and may be sufficient. Also, despite decreasing levels in TAb and SNAb over time, long-term avidity may be a measure worth evaluating and possibly correlating to vaccine efficacy.
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Affiliation(s)
- Sabrina E. Racine-Brzostek
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York, USA
- NewYork-Presbyterian Hospital, Weill Cornell Medical Campus, New York, New York, USA
| | - Jim K. Yee
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York, USA
| | - Ashley Sukhu
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York, USA
| | - Yuqing Qiu
- Department of Population Health Sciences, Weill Cornell Medicine, New York, New York, USA
| | - Sophie Rand
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York, USA
| | - Paul D. Barone
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York, USA
- NewYork-Presbyterian Hospital, Weill Cornell Medical Campus, New York, New York, USA
| | - Ying Hao
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
| | - He S. Yang
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York, USA
- NewYork-Presbyterian Hospital, Weill Cornell Medical Campus, New York, New York, USA
| | - Qing H. Meng
- Department of Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Fred S. Apple
- Departments of Laboratory Medicine and Pathology at Hennepin Healthcare/Hennepin County Medical Center and University of Minnesota, Minneapolis, Minnesota, USA
| | - Yuanyuan Shi
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
- Department of Biomedical Engineering, Shenzhen Research Institute, Beijing University of Chinese Medicine, Shenzhen, China
| | - Amy Chadburn
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York, USA
- NewYork-Presbyterian Hospital, Weill Cornell Medical Campus, New York, New York, USA
| | | | | | - Melissa M. Cushing
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York, USA
- NewYork-Presbyterian Hospital, Weill Cornell Medical Campus, New York, New York, USA
| | - Zhen Zhao
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York, USA
- NewYork-Presbyterian Hospital, Weill Cornell Medical Campus, New York, New York, USA
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12
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Feng C, Shi J, Fan Q, Wang Y, Huang H, Chen F, Tang G, Li Y, Li P, Li J, Cui J, Guo L, Chen S, Jiang M, Feng L, Chen L, Lei C, Ke C, Deng X, Hu F, Tang X, Li F. Protective humoral and cellular immune responses to SARS-CoV-2 persist up to 1 year after recovery. Nat Commun 2021; 12:4984. [PMID: 34404803 PMCID: PMC8370972 DOI: 10.1038/s41467-021-25312-0] [Citation(s) in RCA: 87] [Impact Index Per Article: 21.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2021] [Accepted: 08/02/2021] [Indexed: 02/06/2023] Open
Abstract
SARS-CoV-2 vaccination has been launched worldwide to build effective population-level immunity to curb the spread of this virus. The effectiveness and duration of protective immunity is a critical factor for public health. Here, we report the kinetics of the SARS-CoV-2 specific immune response in 204 individuals up to 1-year after recovery from COVID-19. RBD-IgG and full-length spike-IgG concentrations and serum neutralizing capacity decreases during the first 6-months, but is maintained stably up to 1-year after hospital discharge. Even individuals who had generated high IgG levels during early convalescent stages had IgG levels that had decreased to a similar level one year later. Notably, the RBD-IgG level positively correlates with serum neutralizing capacity, suggesting the representative role of RBD-IgG in predicting serum protection. Moreover, viral-specific cellular immune protection, including spike and nucleoprotein specific, persisted between 6 months and 12 months. Altogether, our study supports the persistence of viral-specific protective immunity over 1 year.
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Affiliation(s)
- Chengqian Feng
- Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China
| | - Jingrong Shi
- Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China
| | - Qinghong Fan
- Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China
| | - Yaping Wang
- Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China
| | - Huang Huang
- Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China
| | - Fengjuan Chen
- Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China
| | - Guofang Tang
- Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China
| | - Youxia Li
- Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China
| | - Pingchao Li
- Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China
| | - Jiaojiao Li
- Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China
| | - Jianping Cui
- Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China
| | - Liliangzi Guo
- Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China
- Department of Gastroenterology, The First Affiliated Hospital, Jinan University, Guangzhou, China
| | - Sisi Chen
- Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China
- Department of Gastroenterology, The First Affiliated Hospital, Jinan University, Guangzhou, China
| | - Mengling Jiang
- Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China
| | - Liqiang Feng
- Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China
| | - Ling Chen
- Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China
- Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China
| | - Chunliang Lei
- Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China
| | - Changwen Ke
- Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, China
| | - Xilong Deng
- Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China.
| | - Fengyu Hu
- Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China.
| | - Xiaoping Tang
- Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China.
| | - Feng Li
- Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China.
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13
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Rosenberg HF, Foster PS. Eosinophils and COVID-19: diagnosis, prognosis, and vaccination strategies. Semin Immunopathol 2021; 43:383-392. [PMID: 33728484 PMCID: PMC7962927 DOI: 10.1007/s00281-021-00850-3] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Accepted: 03/02/2021] [Indexed: 02/07/2023]
Abstract
The unprecedented impact of the coronavirus disease 2019 (COVID-19) pandemic has resulted in global challenges to our health-care systems and our economic security. As such, there has been significant research into all aspects of the disease, including diagnostic biomarkers, associated risk factors, and strategies that might be used for its treatment and prevention. Toward this end, eosinopenia has been identified as one of many factors that might facilitate the diagnosis and prognosis of severe COVID-19. However, this finding is neither definitive nor pathognomonic for COVID-19. While eosinophil-associated conditions have been misdiagnosed as COVID-19 and others are among its reported complications, patients with pre-existing eosinophil-associated disorders (e.g., asthma, eosinophilic gastrointestinal disorders) do not appear to be at increased risk for severe disease; interestingly, several recent studies suggest that a diagnosis of asthma may be associated with some degree of protection. Finally, although vaccine-associated aberrant inflammatory responses, including eosinophil accumulation in the respiratory tract, were observed in preclinical immunization studies targeting the related SARS-CoV and MERS-CoV pathogens, no similar complications have been reported clinically in response to the widespread dissemination of either of the two encapsulated mRNA-based vaccines for COVID-19.
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Affiliation(s)
- Helene F Rosenberg
- National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
| | - Paul S Foster
- School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle and Hunter Medical Research Institute (HMRI), New Lambton Heights, New South Wales, 2300, Australia
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14
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Tripp RA, Stambas J. Intervention Strategies for Seasonal and Emerging Respiratory Viruses with Drugs and Vaccines Targeting Viral Surface Glycoproteins. Viruses 2021; 13:v13040625. [PMID: 33917411 PMCID: PMC8067509 DOI: 10.3390/v13040625] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Revised: 03/31/2021] [Accepted: 04/03/2021] [Indexed: 12/12/2022] Open
Abstract
Vaccines and therapeutics targeting viral surface glycoproteins are a major component of disease prevention for respiratory viral diseases. Over the years, vaccines have proven to be the most successful intervention for preventing disease. Technological advances in vaccine platforms that focus on viral surface glycoproteins have provided solutions for current and emerging pathogens like SARS-CoV-2, and our understanding of the structural basis for antibody neutralization is guiding the selection of other vaccine targets for respiratory viruses like RSV. This review discusses the role of viral surface glycoproteins in disease intervention approaches.
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Affiliation(s)
- Ralph A. Tripp
- Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA 30605, USA
- Correspondence:
| | - John Stambas
- School of Medicine, Geelong Waurn Ponds, Deakin University, Melbourne, VIC 3125, Australia;
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15
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Velikova T. INFECTION-ACQUIRED VERSUS VACCINE-INDUCED IMMUNITY AGAINST COVID-19. CENTRAL ASIAN JOURNAL OF MEDICAL HYPOTHESES AND ETHICS 2021. [DOI: 10.47316/cajmhe.2021.2.1.05] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
The course of COVID-19 depends on a dynamic interplay between SARS-CoV-2 and the host's immune system. Although it is an emerging global health issue, little is known about the specificity, safety, and duration of the immunity elicited by the virus. This hypothesis article explores the benefits of infection-acquired and vaccine-induced immunity against COVID-19, suggesting that the latter outweighs the former. Comparative studies are proposed to explain and reveal all aspects of the immune responses. Although vaccine development relies on studies of naturally acquired immune responses, there are still no comparative analyses of the natural and vaccine immunity against SARS-CoV-2. Moreover, there are scarce reports on the characteristics of both types of responses. The scientific facts about the virulence of SARS-CoV-2 affecting the immune system are of great importance for proposed comparative analyses. Various immunological methods can be employed to elucidate infection-acquired and vaccine-induced immunity against SARS-CoV-2. The safe vaccination of subjects with and without COVID-19 history may disrupt the virus spreading and end the pandemic.
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16
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Decorated and Encapsulated: Virus-Like Particles Against Viral Infections. Vaccines (Basel) 2021; 9:vaccines9030273. [PMID: 33803636 PMCID: PMC8002974 DOI: 10.3390/vaccines9030273] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Accepted: 03/16/2021] [Indexed: 11/17/2022] Open
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