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

Abstract

<jats:p>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.</jats:p>

Peptides for Vaccine Development

“… 183 HBV 15-mer peptide T cell epitopes that bind HLA class II alleles have been predicted using in silico methods. 184 Sette et al. measured peripheral blood lymphocyte levels of patients with acute hepatitis to probe the antigenicity of ca .…”

Innate and adaptive immune escape mechanisms of hepatitis B virus

“…Compared to HLA-DP and HLA-DQ, HLA-DR allele containing an extra β-chain gene whose product can pair with the DRα chain on APCs, is more important for the induction of sustained HBV-specific immune response. Upon HBV infection, single nucleotide polymorphisms of HLA-II antigens may also contribute to the induction of immune tolerance, leading to persistent HBV infection[ 57 , 59 - 62 ]. HBV infection reduces the expression of HLA-DP and HLA-DQ molecules on APCs, which in turn results in impaired antigen presentation capacity and an inefficient T-cell response[ 12 , 13 ].…”

Subunit Vaccine Against Sars-Cov-2 Using CTL and HTL Epitopes

“…Toxicity is referred to as peptides, molecules, or protein that are capable of producing illness on interaction with body muscles coupling with genetic macromolecular such as cellular receptor or enzymes. For designing a potential vaccine structure it's mandatory to check toxicity [40].As shown in table 4, in order to check the toxicity all antigenic epitopes were screened.…”