Toleration of amino acid substitutions within hepatitis B virus envelope protein epitopes established by peptide replacement set analysis. II. Region S(122-136)

Abstract

The envelope of the hepatitis B virus (HBV) consists of three related proteins, designated S-, M- and L-protein, all of which share a common 226-amino acid residue sequence, corresponding to the S-protein that is sufficient for eliciting protective immunity against HBV. HBV variants, resulting from point mutations leading to replacements of amino acids within the S(122-160) segment of S-protein, have been recently recognized. In order to assure the continued success of vaccination against HBV and the adequacy of diagnostic tests for HBV envelope antigens and antibodies, it is necessary to understand the impact of amino acid replacements on the immunological recognition of S-protein at both the B- and T-cell levels. Immunologically tolerated and forbidden amino acid replacements within the S(139-147) segment of S-protein have already been discerned. The impact of amino acid substitutions within the S(122-136) segment on the immunological recognition of S-protein is analyzed in this report. Such replacements do not appreciably affect the binding of rabbit and goat anti-S antibodies to replacement set peptides, while decreased murine antibody binding was observed with some peptides having substitutions at residues 122, 123 and 133. On the other hand, amino acid substitutions within the (126-136) region, except those distinguishing serological subtypes of HBV from each other, abrogated murine T-cell proliferative responses to the peptides, while substitutions at residues 122, 123 and 125 had a lesser effect. Some of the peptides with amino acid substitutions peculiar to the variants had diminished stimulatory activity for T-cells from individuals vaccinated against hepatitis B. Amino acid substitutions in both the S(139-147) and S(122-136) segments of S-protein may potentially result in variant viruses escaping immunological surveillance based on current hepatitis B vaccines.