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Ishwarlall TZ, Adeleke VT, Maharaj L, Okpeku M, Adeniyi AA, Adeleke MA. Multi-epitope vaccine candidates based on mycobacterial membrane protein large (MmpL) proteins against Mycobacterium ulcerans. Open Biol 2023; 13:230330. [PMID: 37935359 PMCID: PMC10645115 DOI: 10.1098/rsob.230330] [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: 09/08/2023] [Accepted: 09/26/2023] [Indexed: 11/09/2023] Open
Abstract
Buruli ulcer (BU) is a neglected tropical disease. It is caused by the bacterium Mycobacterium ulcerans and is characterized by skin lesions. Several studies were performed testing the Bacillus Calmette-Guérin (BCG) vaccine in human and animal models and M. ulcerans-specific vaccines in animal models. However, there are currently no clinically accepted vaccines to prevent M. ulcerans infection. The aim of this study was to identify T-cell and B-cell epitopes from the mycobacterial membrane protein large (MmpL) proteins of M. ulcerans. These epitopes were analysed for properties including antigenicity, immunogenicity, non-allergenicity, non-toxicity, population coverage and the potential to induce cytokines. The final 8 CD8+, 12 CD4+ T-cell and 5 B-cell epitopes were antigenic, non-allergenic and non-toxic. The estimated global population coverage of the CD8+ and CD4+ epitopes was 97.71%. These epitopes were used to construct five multi-epitope vaccine constructs with different adjuvants and linker combinations. The constructs underwent further structural analyses and refinement. The constructs were then docked with Toll-like receptors. Three of the successfully docked complexes were structurally analysed. Two of the docked complexes successfully underwent molecular dynamics simulations (MDS) and post-MDS analysis. The complexes generated were found to be stable. However, experimental validation of the complexes is required.
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Affiliation(s)
- Tamara Z. Ishwarlall
- Discipline of Genetics, School of Life Sciences, University of KwaZulu-Natal, Durban, South Africa
| | - Victoria T. Adeleke
- Department of Chemical Engineering, Mangosuthu University of Technology, Umlazi, Durban, South Africa
| | - Leah Maharaj
- Discipline of Genetics, School of Life Sciences, University of KwaZulu-Natal, Durban, South Africa
| | - Moses Okpeku
- Discipline of Genetics, School of Life Sciences, University of KwaZulu-Natal, Durban, South Africa
| | - Adebayo A. Adeniyi
- Department of Chemistry, Faculty of Natural and Agricultural Sciences, University of the Free State, Bloemfontein, South Africa
- Department of Industrial Chemistry, Federal University Oye Ekiti, Ekiti State, Nigeria
| | - Matthew A. Adeleke
- Discipline of Genetics, School of Life Sciences, University of KwaZulu-Natal, Durban, South Africa
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Alharbi M, Alshammari A, Alasmari AF, Alharbi S, Tahir ul Qamar M, Abbasi SW, Shaker B, Ahmad S. Whole Proteome-Based Therapeutic Targets Annotation and Designing of Multi-Epitope-Based Vaccines against the Gram-Negative XDR- Alcaligenes faecalis Bacterium. Vaccines (Basel) 2022; 10:462. [PMID: 35335094 PMCID: PMC8955209 DOI: 10.3390/vaccines10030462] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2022] [Revised: 03/11/2022] [Accepted: 03/14/2022] [Indexed: 12/29/2022] Open
Abstract
This study involved therapeutic targets mining for the extremely drug-resistant bacterial species called Alcaligenes faecalis, which is known to infect humans. The infections caused by this species in different parts of the human body have been linked with a higher degree of resistance to several classes of antibiotics. Meanwhile, alternate therapeutic options are needed to treat these bacterial infections in clinical settings. In the current study, a subtractive proteomics approach was adapted to annotate the whole proteome of Alcaligenes faecalis and prioritize target proteins for vaccine-related therapeutics design. This was followed by targeted protein-specific immune epitope prediction and prioritization. The shortlisted epitopes were further subjected to structural design and in silico validation of putative vaccines against Alcaligenes faecalis. The final vaccine designs were also evaluated for potential interaction analysis with human TLR-2 through molecular docking. Finally, the putative vaccines were subjected to in silico cloning and immune simulation approaches to ensure the feasibility of the target-specific vaccine constructs in further experimental designs.
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Affiliation(s)
- Metab Alharbi
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia; (M.A.); (A.A.); (A.F.A.)
| | - Abdulrahman Alshammari
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia; (M.A.); (A.A.); (A.F.A.)
| | - Abdullah F. Alasmari
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia; (M.A.); (A.A.); (A.F.A.)
| | | | - Muhammad Tahir ul Qamar
- Department of Bioinformatics and Biotechnology, Government College University, Faisalabad 38000, Pakistan
| | - Sumra Wajid Abbasi
- NUMS Department of Biological Sciences, National University of Medical Sciences, Rawalpindi 46000, Pakistan;
| | - Bilal Shaker
- Department of Biomedical Engineering, Chung-Ang University, 84 Heukseok-ro, Dongjak-gu, Seoul 06974, Korea;
| | - Sajjad Ahmad
- Department of Health and Biological Sciences, Abasyn University, Peshawar 25000, Pakistan
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Song Q, Sun XF, Wu XL, Dong Y, Wang L. Skeletal muscle metastases of hepatocellular carcinoma: A case report and literature review. World J Clin Cases 2021; 9:3334-3341. [PMID: 34002142 PMCID: PMC8107905 DOI: 10.12998/wjcc.v9.i14.3334] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Revised: 12/24/2020] [Accepted: 01/07/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The metastasis of liver cancer to skeletal muscle is extremely rare compared to other sites. We herein report a case of rapidly developing skeletal metastases following liver transplantation due to primary liver cancer.
CASE SUMMARY A 70-year-old male with underlying chronic hepatitis B virus infection was diagnosed with hepatocellular carcinoma (HCC), for which he underwent liver transplantation in 2014. Six years after receiving the transplant, pathological examination confirmed the presence of HCC without vascular invasion. He was admitted to the hospital with a rapidly growing mass on his right thigh. Ultrasound examination revealed a mixed echo mass in the lateral soft tissue of the middle part of the right femur. Magnetic resonance imaging showed heterogeneous iso-signal intensity on T1-weighted images and heterogeneous hyper-intensity on T2-weighted images compared to the surrounding muscles. Pathological examination of the ultrasound-guided needle biopsy specimen revealed that it was similar to the previously detected liver cancer; the diagnosis was metastasis of HCC. Surgical excision was performed. There were no other sites of metastasis, and the patient recovered well after surgery.
CONCLUSION This report presents a rare case of skeletal metastasis following liver transplantation for HCC. The study suggests a possible role for skeletal muscle metastasis mechanisms, which should be the focus of future research.
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Affiliation(s)
- Qi Song
- Department of Ultrasound, Bethune First Hospital of Jilin University, Changchun 130000, Jilin Province, China
| | - Xiao-Feng Sun
- Department of Ultrasound, Bethune First Hospital of Jilin University, Changchun 130000, Jilin Province, China
| | - Xiao-Li Wu
- Department of Ultrasound, Bethune First Hospital of Jilin University, Changchun 130000, Jilin Province, China
| | - Yi Dong
- Department of Ultrasound, Bethune First Hospital of Jilin University, Changchun 130000, Jilin Province, China
| | - Le Wang
- Department of Ultrasound, Bethune First Hospital of Jilin University, Changchun 130000, Jilin Province, China
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Kanza S, Graham Frey J. Semantic Technologies in Drug Discovery. SYSTEMS MEDICINE 2021. [DOI: 10.1016/b978-0-12-801238-3.11520-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022] Open
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Kengne-Ouafo JA, Sutherland CJ, Binka FN, Awandare GA, Urban BC, Dinko B. Immune Responses to the Sexual Stages of Plasmodium falciparum Parasites. Front Immunol 2019; 10:136. [PMID: 30804940 PMCID: PMC6378314 DOI: 10.3389/fimmu.2019.00136] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2018] [Accepted: 01/16/2019] [Indexed: 11/13/2022] Open
Abstract
Malaria infections remain a serious global health problem in the world, particularly among children and pregnant women in Sub-Saharan Africa. Moreover, malaria control and elimination is hampered by rapid development of resistance by the parasite and the vector to commonly used antimalarial drugs and insecticides, respectively. Therefore, vaccine-based strategies are sorely needed, including those designed to interrupt disease transmission. However, a prerequisite for such a vaccine strategy is the understanding of both the human and vector immune responses to parasite developmental stages involved in parasite transmission in both man and mosquito. Here, we review the naturally acquired humoral and cellular responses to sexual stages of the parasite while in the human host and the Anopheles vector. In addition, updates on current anti-gametocyte, anti-gamete, and anti-mosquito transmission blocking vaccines are given. We conclude with our views on some important future directions of research into P. falciparum sexual stage immunity relevant to the search for the most appropriate transmission-blocking vaccine.
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Affiliation(s)
- Jonas A Kengne-Ouafo
- West African Centre for Cell Biology of Infectious Pathogens, University of Ghana, Accra, Ghana
| | - Colin J Sutherland
- Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom
| | - Fred N Binka
- Department of Epidemiology and Biostatistics, School of Public Health, University of Health and Allied Sciences, Ho, Ghana
| | - Gordon A Awandare
- West African Centre for Cell Biology of Infectious Pathogens, University of Ghana, Accra, Ghana
| | - Britta C Urban
- Faculty of Biological Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom
| | - Bismarck Dinko
- Department of Biomedical Sciences, School of Basic and Biomedical Sciences, University of Health and Allied Sciences, Ho, Ghana
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Bah SY, Morang'a CM, Kengne-Ouafo JA, Amenga-Etego L, Awandare GA. Highlights on the Application of Genomics and Bioinformatics in the Fight Against Infectious Diseases: Challenges and Opportunities in Africa. Front Genet 2018; 9:575. [PMID: 30538723 PMCID: PMC6277583 DOI: 10.3389/fgene.2018.00575] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2018] [Accepted: 11/08/2018] [Indexed: 01/18/2023] Open
Abstract
Genomics and bioinformatics are increasingly contributing to our understanding of infectious diseases caused by bacterial pathogens such as Mycobacterium tuberculosis and parasites such as Plasmodium falciparum. This ranges from investigations of disease outbreaks and pathogenesis, host and pathogen genomic variation, and host immune evasion mechanisms to identification of potential diagnostic markers and vaccine targets. High throughput genomics data generated from pathogens and animal models can be combined with host genomics and patients’ health records to give advice on treatment options as well as potential drug and vaccine interactions. However, despite accounting for the highest burden of infectious diseases, Africa has the lowest research output on infectious disease genomics. Here we review the contributions of genomics and bioinformatics to the management of infectious diseases of serious public health concern in Africa including tuberculosis (TB), dengue fever, malaria and filariasis. Furthermore, we discuss how genomics and bioinformatics can be applied to identify drug and vaccine targets. We conclude by identifying challenges to genomics research in Africa and highlighting how these can be overcome where possible.
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Affiliation(s)
- Saikou Y Bah
- West African Centre for Cell Biology of Infectious Pathogens, University of Ghana, Accra, Ghana.,Vaccine and Immunity Theme, MRC Unit The Gambia at London School of Hygiene & Tropical Medicine, Banjul, Gambia
| | - Collins Misita Morang'a
- West African Centre for Cell Biology of Infectious Pathogens, University of Ghana, Accra, Ghana
| | - Jonas A Kengne-Ouafo
- West African Centre for Cell Biology of Infectious Pathogens, University of Ghana, Accra, Ghana
| | - Lucas Amenga-Etego
- West African Centre for Cell Biology of Infectious Pathogens, University of Ghana, Accra, Ghana
| | - Gordon A Awandare
- West African Centre for Cell Biology of Infectious Pathogens, University of Ghana, Accra, Ghana
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Mirzaei N, Poursina F, Moghim S, Rashidi N, Ghasemian Safaei H. The study of H. pylori putative candidate factors for single- and multi-component vaccine development. Crit Rev Microbiol 2017; 43:631-650. [PMID: 28581361 DOI: 10.1080/1040841x.2017.1291578] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Helicobacter pylori has grown to colonize inside the stomach of nearly half of the world's population, turning into the most prevalent infections in the universe. Medical care failures noticeably confirm the need for a vaccine to hinder or deal with H. pylori. This review is planned to discuss the most known factors as a vaccine candidate, including single (AhpC, BG, CagA, KatA, Fla, Hsp, HWC, Lpp, LPS, NAP, OMP, OMV, SOD, Tpx, Urease, VacA) and multi-component vaccines. Many promising results in the field of single and multivalent vaccine can be seen, but there is no satisfactory outcome and neither a prophylactic nor a therapeutic vaccine to treat or eradicate the infection in human has been acquired. Hence, selecting suitable antigen is an important factor as an appropriate adjuvant. Taken all together, the development of efficient anti-H. pylori vaccines relies on the fully understanding of the interactions between H. pylori and its host immune system. Therefore, more work should be done on epitope mapping, analysis of molecular structure, and determination of the antigen determinant region as well due to design a vaccine, preferably a multi-component vaccine to elicit specific CD4 T-cell responses that are required for H. pylori vaccine efficacy.
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Affiliation(s)
- Nasrin Mirzaei
- a Department of Microbiology , Tonekabon Branch, Islamic Azad University , Tonekabon , Iran
| | - Farkhondeh Poursina
- b Department of Microbiology , Isfahan University of Medical Sciences , Isfahan , Iran
| | - Sharareh Moghim
- b Department of Microbiology , Isfahan University of Medical Sciences , Isfahan , Iran
| | - Niloufar Rashidi
- c Department of Laboratory Sciences , Ahvaz University of Medical Sciences , Ahvaz , Iran
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Yan SK, Liu RH, Jin HZ, Liu XR, Ye J, Shan L, Zhang WD. "Omics" in pharmaceutical research: overview, applications, challenges, and future perspectives. Chin J Nat Med 2015; 13:3-21. [PMID: 25660284 DOI: 10.1016/s1875-5364(15)60002-4] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2014] [Indexed: 12/18/2022]
Abstract
In the post-genomic era, biological studies are characterized by the rapid development and wide application of a series of "omics" technologies, including genomics, proteomics, metabolomics, transcriptomics, lipidomics, cytomics, metallomics, ionomics, interactomics, and phenomics. These "omics" are often based on global analyses of biological samples using high through-put analytical approaches and bioinformatics and may provide new insights into biological phenomena. In this paper, the development and advances in these omics made in the past decades are reviewed, especially genomics, transcriptomics, proteomics and metabolomics; the applications of omics technologies in pharmaceutical research are then summarized in the fields of drug target discovery, toxicity evaluation, personalized medicine, and traditional Chinese medicine; and finally, the limitations of omics are discussed, along with the future challenges associated with the multi-omics data processing, dynamics omics analysis, and analytical approaches, as well as amenable solutions and future prospects.
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Affiliation(s)
- Shi-Kai Yan
- School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Run-Hui Liu
- School of Pharmacy, Second Military Medical University, Shanghai 200433, China
| | - Hui-Zi Jin
- School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Xin-Ru Liu
- School of Pharmacy, Second Military Medical University, Shanghai 200433, China
| | - Ji Ye
- School of Pharmacy, Second Military Medical University, Shanghai 200433, China
| | - Lei Shan
- School of Pharmacy, Second Military Medical University, Shanghai 200433, China
| | - Wei-Dong Zhang
- School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China; School of Pharmacy, Second Military Medical University, Shanghai 200433, China; Shanghai Institute of Pharmaceutical Industry, Shanghai 200040, China.
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