In Silico Prediction of Human Leukocytes Antigen (HLA) Class II Binding Hepatitis B Virus (HBV) Peptides in Botswana.

Wonderful Tatenda Choga,Peter Opiyo Kimathi,Kaelo K Seatla,Sikhulile Moyo,Rosemary M Musonda,Motswedi Anderson,Jason T Blackard,Bonolo B Phinius,Edward Zumbika,Simani Gaseitsiwe,Lynnette N Bhebhe,Tshepiso Mbangiwa,Kabo Baruti,Trevor Graham Bell

doi:10.3390/v12070731

Abstract

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 (epi) 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 (PreS/S) from Botswana were used. Of the 1819 epi bindings predicted, 20.2% were strong binders (SB), and none of the putative epi 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 epi predicted from the 3 proteins and amongst, S regions had the highest number of epi (n = 186). Epitope-densities (Depi) 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.

Highlights

Hepatitis B virus (HBV), a member of the Hepadnaviradae family, is the major etiology of end stage liver diseases (ESLD), liver cirrhosis (LC) and hepatocellular carcinoma (HCC), and causes up to 887,000 deaths per year [1]
Their success is affected by virus evolution within known protective epitopes; multi-epitope, population-based vaccine constructs are preferred in order to generate a potent immunologic response against HBV
We demonstrate the quality of T cell epitopes among different HBV genotypes and reconstructed a candidate multi-epitope population-based vaccine

Summary

Introduction

Hepatitis B virus (HBV), a member of the Hepadnaviradae family, is the major etiology of end stage liver diseases (ESLD), liver cirrhosis (LC) and hepatocellular carcinoma (HCC), and causes up to 887,000 deaths per year [1]. Viral clearance is mediated by cytokines, lymphocytes, and the ability to mount a multi-specific polyclonal and vigorous T cell-mediated response against HBV antigens for a protective immunity [3,4,5]. The major histocompatibility complexes (MHCs)—known as human leukocytes antigens (HLAs) in humans—are integral components of host genes located at chromosome 6p21. These highly polymorphic proteins serve as mediators of adaptive immune responses by presenting processed antigenic peptides to T cells. The MHC class II alleles (HLA-DR, -DQ and -DP) present epitopes to CD4+ T cells [epi-HLA class II → CD4+ T-cells]

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