Antibodies recognizing human serum albumin are not elicited by immunization with preS2 sequences of the hepatitis B virus envelope protein

Antibodies to the preS2 region of the hepatitis B virus (HBV) envelope protein and to human serum albumin (HSA) were allegedly detected at about the same level in sera of humans with acute or chronic hepatitis B [Hellstr?m et al., 1986]. It was claimed that anti-HSA arises as a result of an immune response to the preS2 sequence and that it was involved in hepatocellular damage. Over 100 sera from animals and humans immunized with HBsAg containing preS2 sequences, or with synthetic peptides from the preS1, preS2, and S regions of the HBV env protein were assayed for anti-HSA. The results revealed the following: 1) Immunization with the native preS2 sequence or with unconjugated synthetic peptides derived from that sequence does not result in elicitation of anti-HSA. Therefore the alleged appearance of anti-HSA during hepatitis B cannot be directly related to an anti-preS2-specific immune response. 2) Some synthetic peptides, whether or not they were derived from the preS2 sequence, when linked to certain carriers, but not to others, elicited in rabbits an anti-HSA response, which was markedly lower than the response to the homologous peptide. These anti-HSA antibodies could be separated from anti-preS2-specific antibodies by affinity chromatography and did not recognize the synthetic peptide used for immunization. The use in active immunoprophylaxis of hepatitis B of unconjugated peptides from the preS2 sequence with proven high immunogenicity will avoid carrier/linker-mediated induction of antibodies not relevant to protection against HBV.