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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Main Authors: 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
Format: Article
Language:English
Published: MDPI AG 2020-07-01
Series:Viruses
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Online Access:https://www.mdpi.com/1999-4915/12/7/731
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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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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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