Absence of pre-S2 antibodies in natural hepatitis B virus infection

Antibodies to the host "self" component human serum albumin (HSA) and to its receptor are induced by the pre-S2 encoded aminoacid sequence (120-145) of the middle surface protein on the hepatitis B virus (HBV) particle and are produced as part of the immune response during acute HBV-infection. The antibodies disappeared rapidly during the convalescence phase and were not detectable in patients with naturally acquired immunity to HB. These data raise questions about the importance of anti-pre-S2 antibodies for long-term protection against HBV-infection. The coexistence of HBV-DNA with antibodies to native HSA (nHSA) in 13/16 patients with biopsy proven liver disease and of HBV-DNA with anti-pre-S2 in 10/13 patients argues against the attribution of virus eliminating properties to antibodies directed against pre-S2 determinants. In fact circulating anti-nHSA and anti-pre-S2 persisted in 16/17 and 13/17 patients, respectively, with major HBV-induced liver disease but not in symptomless HBsAg carriers. This finding suggests that continuous production of antibodies against the "self" component HSA and/or its receptor structures are associated with the pathogenesis of chronic HBV-induced liver disease. Pre-S2 coded peptide sequences should thus not be incorporated into HB vaccines.