Immunological cross-reactivity between preS2 sequences of the hepatitis B virus envelope proteins corresponding to serological subtypes adw2 and ayw

An immune response to epitopes localized on the preS region of the hepatitis B virus (HBV) envelope (env) is elicited during recovery from HBV infection and appears to play a role in virus clearance. Anti-preS antibodies (Ab) are expected to be protective against HBV infection as indicated by the virus-neutralizing capacity of Ab to a preS2-specific synthetic peptide preS(120–145). However, there is considerable amino acid variability between preS regions corresponding to distinct serological subtypes of HBV, raising the question whether the preS sequences are sufficiently related immunologically to have the potential of inducing cross-protective immunity. To answer this question concerning the preS2 region, antisera to synthetic peptides preS(120–153) and preS(128–153) corresponding to subtypes adw2and ayw, as well as to the native env [ ayw] protein were raised. Using the resulting polyclonal Ab, an immunological relatedness between preS2 sequences of subtypes adw2 and ayw was demonstrated. On the other hand, Ab selected by affinity chromatography or by cloning hybridoma cells may recognize with strong preference subtype-specific determinants within the preS2 region when the compared antigens are in solution rather than on the solid phase. These findings have implication for the design of: (1) preS2-specific immunogens and (2) immunoassays for quantitation of preS2 sequences in HBV env proteins.