Hepatitis B virus e antigen specific epitopes and limitations of commercial anti-HBe immunoassays

Current commercial hepatitis B virus (HBV) anti-HBe immunoassays are design ed so that anti-HBe is detectable only in the absence of excess HBeAg. Rece ntly, with the use of direct anti-HBe assays, anti-HBe was detected in indi viduals who had been seropositive for several years for HBeAg [Maruyama et at. (1993) J. Clin. Invest. 91:2586-2595]. Although anti-HBe seroconversion does not necessarily indicate subsequent HBeAg clearance, the ability to d etect earlier anti-HBe seroconversion could have clinical significance for monitoring patients undergoing HBV immunotherapy (e.g., alpha interferon th erapy). Because the HBeAg and the HBcAg share 149 amino acids, an anti-HBe assay must distinguish anti-HBe from anti-HBc antibodies. Although the HBV HBeAg and HBcAg display distinct immunogenic determinants, much remains unk nown regarding the complete epitope spectrum specific to each antigen. The goal of this study was 3-fold. The first objective was to identify HBeAg sp ecific linear epitopes. The second objective was to design an anti-HBe immu noassay capable of detecting anti-HBe specific antibody in the presence of excess HBeAg. The third objective was to characterize early anti-HBe seroco nversion antibodies. The major linear epitope residing in the HBeAg amino a cid sequence was mapped and 2 novel minor epitopes (delta, gamma) which app ear to be HBeAg specific have been identified. An anti-HBe immunoassay capa ble of detecting anti-HBe specific antibody in the presence of excess HBeAg was designed. Finally, it was found that early anti-HBe seroconversion ant ibodies appear to be conformational, whereas later seroconversion, more typ ically associated with the clearance of HBeAg, is characterized by the pres ence of antibodies to the linear HBeAg epitopes. J. Med. Virol. 60:256-263, 2000. (C) 2000 Wiley-Liss, Inc.