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Abstract There is still no cure for chronic hepatitis B virus infection (CHBV), a major cause of liver cancers and related malignancies. Elucidating the role of CD4+ T-helper cells in activating immunological responses that clear antigenic peptides during primary HBV infection holds a potential strategy for developing potent vaccines. Since the strength of CD4+ T cell responses is dictated by binding of viral epitopes to class-II human leukocyte antigens (HLAs), we hypothesize that the quality of immunological responses in CHBV patients is influenced by host genetics and HBV genotypes. Here, ninety-two non-recombinant complete HBV surface-gene proteins (PreS1/S) from Botswana were sequenced (genotype A 44(47.8%); D 48(52.2%)) and 15-mer binding epitopes restricted to nine HLA-class II molecules (DRB5/1) were mapped in silico. The HLAs used have high population coverage in Botswana. The total predicted epitopes per HLA were 94-(genotype A) and 105-(genotype D) for PreS1, 42 (A and D) for PreS2, and 105 (A and D) for S. Epitope densities (binding peptides to total epitopes) were 3 per cent and 6 per cent (PreS1A&D), 4 per cent and 2 per cent (PreS2A&D), and 23 per cent and 22 per cent (S1A&D). SA&D proteins had most polytopes: CPGYRWMCLRRFII66-81, PGYRWMCLRRFIIF67-82, GYRWMCLRRFIIFL68-83, and YRWMCLRRFIIFLF69-84 binding to 5 (55.6%) HLAs (DRB1*0101/0701/1101/1501 and DRB5*0101) used. HLA-DRB*0101 bound the most epitopes, and the least were bound by HLA-DRB*0302/0701/0401 for both genotypes. PreS1D polytope: PAFRANTANPDWDFN32-46 binds to DRB1*0101/0401/1302 and PreS2 polytopes: TAFHQALQDPRVRG6-19 and AFHQALQDPRVRGL7-20 bind to DRB1*010/1501 alleles. Non-synonymous mutations impair peptide-HLA binding when assessed as combinations of > 2. The least active HLAs may be associated with CHBV and vice-versa for HBV clearance, thus the algorithm may be used to predict HBV prognosis for different haplotypes. The results favor the use of epitopes from S protein as broad genotype vaccine. This study highlights the need to explore further the mechanisms of PreS1 and its effect on the immune system.

A25 Impact of polymorphism in the hepatitis B surface gene on human leukocyte antigen (HLA) class II