In Silico Prediction of Human Leukocytes Antigen (HLA) Class II Binding Hepatitis B Virus (HBV) Peptides in Botswana
Hepatitis B virus (HBV) is the primary cause of liver-related malignancies worldwide, and there is no effective cure for chronic HBV infection (CHB) currently. Strong immunological responses induced by T cells are associated with HBV clearance during acute infection; however, the repertoire of epito...
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author | Wonderful Tatenda Choga Motswedi Anderson Edward Zumbika Bonolo B. Phinius Tshepiso Mbangiwa Lynnette N. Bhebhe Kabo Baruti Peter Opiyo Kimathi Kaelo K. Seatla Rosemary M. Musonda Trevor Graham Bell Sikhulile Moyo Jason T. Blackard Simani Gaseitsiwe |
author_facet | Wonderful Tatenda Choga Motswedi Anderson Edward Zumbika Bonolo B. Phinius Tshepiso Mbangiwa Lynnette N. Bhebhe Kabo Baruti Peter Opiyo Kimathi Kaelo K. Seatla Rosemary M. Musonda Trevor Graham Bell Sikhulile Moyo Jason T. Blackard Simani Gaseitsiwe |
author_sort | Wonderful Tatenda Choga |
collection | DOAJ |
description | Hepatitis B virus (HBV) is the primary cause of liver-related malignancies worldwide, and there is no effective cure for chronic HBV infection (CHB) currently. Strong immunological responses induced by T cells are associated with HBV clearance during acute infection; however, the repertoire of epitopes (<i>epi</i>) presented by major histocompatibility complexes (MHCs) to elicit these responses in various African populations is not well understood. In silico approaches were used to map and investigate 15-mers HBV peptides restricted to 9 HLA class II alleles with high population coverage in Botswana. Sequences from 44 HBV genotype A and 48 genotype D surface genes (<i>PreS/S</i>) from Botswana were used. Of the 1819 <i>epi</i> bindings predicted, 20.2% were strong binders (SB), and none of the putative <i>epi</i> bind to all the 9 alleles suggesting that multi-epitope, genotype-based, population-based vaccines will be more effective against HBV infections as opposed to previously proposed broad potency epitope-vaccines which were assumed to work for all alleles. In total, there were 297 unique <i>epi</i> predicted from the 3 proteins and amongst, S regions had the highest number of <i>epi</i> (n = 186). Epitope-densities (D<sub>epi</sub>) between genotypes A and D were similar. A number of mutations that hindered HLA-peptide binding were observed. We also identified antigenic and genotype-specific peptides with characteristics that are well suited for the development of sensitive diagnostic kits. This study identified candidate peptides that can be used for developing multi-epitope vaccines and highly sensitive diagnostic kits against HBV infection in an African population. Our results suggest that viral variability may hinder HBV peptide-MHC binding, required to initiate a cascade of immunological responses against infection. |
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issn | 1999-4915 |
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spelling | doaj.art-24e226cc26634f6c9b89f51b7b69720b2023-11-20T05:57:37ZengMDPI AGViruses1999-49152020-07-0112773110.3390/v12070731In Silico Prediction of Human Leukocytes Antigen (HLA) Class II Binding Hepatitis B Virus (HBV) Peptides in BotswanaWonderful Tatenda Choga0Motswedi Anderson1Edward Zumbika2Bonolo B. Phinius3Tshepiso Mbangiwa4Lynnette N. Bhebhe5Kabo Baruti6Peter Opiyo Kimathi7Kaelo K. Seatla8Rosemary M. Musonda9Trevor Graham Bell10Sikhulile Moyo11Jason T. Blackard12Simani Gaseitsiwe13Research Laboratory, Botswana Harvard AIDS Institute Partnership, Gaborone 0000, BotswanaResearch Laboratory, Botswana Harvard AIDS Institute Partnership, Gaborone 0000, BotswanaDepartment of Applied Biology and Biochemistry, Faculty of Applied Sciences, National University of Science and Technology, Bulawayo 0000, ZimbabweResearch Laboratory, Botswana Harvard AIDS Institute Partnership, Gaborone 0000, BotswanaResearch Laboratory, Botswana Harvard AIDS Institute Partnership, Gaborone 0000, BotswanaResearch Laboratory, Botswana Harvard AIDS Institute Partnership, Gaborone 0000, BotswanaResearch Laboratory, Botswana Harvard AIDS Institute Partnership, Gaborone 0000, BotswanaCentre for Proteomic and Genomic Research, Cape Town 7925, South AfricaResearch Laboratory, Botswana Harvard AIDS Institute Partnership, Gaborone 0000, BotswanaResearch Laboratory, Botswana Harvard AIDS Institute Partnership, Gaborone 0000, BotswanaIndependent Researcher, P.O. Box 497, Wits, Johannesburg 2050, South AfricaResearch Laboratory, Botswana Harvard AIDS Institute Partnership, Gaborone 0000, BotswanaDivision of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USAResearch Laboratory, Botswana Harvard AIDS Institute Partnership, Gaborone 0000, BotswanaHepatitis B virus (HBV) is the primary cause of liver-related malignancies worldwide, and there is no effective cure for chronic HBV infection (CHB) currently. Strong immunological responses induced by T cells are associated with HBV clearance during acute infection; however, the repertoire of epitopes (<i>epi</i>) presented by major histocompatibility complexes (MHCs) to elicit these responses in various African populations is not well understood. In silico approaches were used to map and investigate 15-mers HBV peptides restricted to 9 HLA class II alleles with high population coverage in Botswana. Sequences from 44 HBV genotype A and 48 genotype D surface genes (<i>PreS/S</i>) from Botswana were used. Of the 1819 <i>epi</i> bindings predicted, 20.2% were strong binders (SB), and none of the putative <i>epi</i> bind to all the 9 alleles suggesting that multi-epitope, genotype-based, population-based vaccines will be more effective against HBV infections as opposed to previously proposed broad potency epitope-vaccines which were assumed to work for all alleles. In total, there were 297 unique <i>epi</i> predicted from the 3 proteins and amongst, S regions had the highest number of <i>epi</i> (n = 186). Epitope-densities (D<sub>epi</sub>) between genotypes A and D were similar. A number of mutations that hindered HLA-peptide binding were observed. We also identified antigenic and genotype-specific peptides with characteristics that are well suited for the development of sensitive diagnostic kits. This study identified candidate peptides that can be used for developing multi-epitope vaccines and highly sensitive diagnostic kits against HBV infection in an African population. Our results suggest that viral variability may hinder HBV peptide-MHC binding, required to initiate a cascade of immunological responses against infection.https://www.mdpi.com/1999-4915/12/7/731hepatitis B virus (HBV)HLA class II allelesT-cell epitopesin silicoimmunoinformaticscandidate multi-epitope vaccines (MEV) |
spellingShingle | Wonderful Tatenda Choga Motswedi Anderson Edward Zumbika Bonolo B. Phinius Tshepiso Mbangiwa Lynnette N. Bhebhe Kabo Baruti Peter Opiyo Kimathi Kaelo K. Seatla Rosemary M. Musonda Trevor Graham Bell Sikhulile Moyo Jason T. Blackard Simani Gaseitsiwe In Silico Prediction of Human Leukocytes Antigen (HLA) Class II Binding Hepatitis B Virus (HBV) Peptides in Botswana Viruses hepatitis B virus (HBV) HLA class II alleles T-cell epitopes in silico immunoinformatics candidate multi-epitope vaccines (MEV) |
title | In Silico Prediction of Human Leukocytes Antigen (HLA) Class II Binding Hepatitis B Virus (HBV) Peptides in Botswana |
title_full | In Silico Prediction of Human Leukocytes Antigen (HLA) Class II Binding Hepatitis B Virus (HBV) Peptides in Botswana |
title_fullStr | In Silico Prediction of Human Leukocytes Antigen (HLA) Class II Binding Hepatitis B Virus (HBV) Peptides in Botswana |
title_full_unstemmed | In Silico Prediction of Human Leukocytes Antigen (HLA) Class II Binding Hepatitis B Virus (HBV) Peptides in Botswana |
title_short | In Silico Prediction of Human Leukocytes Antigen (HLA) Class II Binding Hepatitis B Virus (HBV) Peptides in Botswana |
title_sort | in silico prediction of human leukocytes antigen hla class ii binding hepatitis b virus hbv peptides in botswana |
topic | hepatitis B virus (HBV) HLA class II alleles T-cell epitopes in silico immunoinformatics candidate multi-epitope vaccines (MEV) |
url | https://www.mdpi.com/1999-4915/12/7/731 |
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