Determination of the Protective Effects of Neutralizing Anti‐Hepatitis B Virus (HBV) Immunoglobulins by Epitope Mapping with Recombinant HBV Surface‐Antigen Proteins

Abstract

Anti-hepatitis B virus (HBV) surface-antigen immunoglobulins prepared from human sera are clinical reagents which have been approved for prophylactic treatment in HBV-exposed persons. The passive immunoprophylaxis with immunoglobulins is meant to cross-link viral particles, which are then further cleared by the host's own immune system. While antibodies specific for both anti-S-and anti-preS proteins have been proved to serve as effective anti-viral agents, so far the fine antigen specificity of clinical immunoglobulin preparations has not been determined. Using recombinant proteins covering the hepatitis B surface antigen, in the present study, the specificity of a commercially available immunoglobulin preparation was determined and immunodominant epitopes were mapped. Here, it is shown that the major reactivity of anti-HBV immunoglobulins is directed against the S-protein, and that no reactivity to the preS2 but a weak binding activity to the preS1 region was detectable. The antigen reactivity within the preS1 region was biased to the C-terminal region, which indicates the presence of a putative B-cell epitope. The evaluation of the antigen specificity and determination of novel protective epitopes will provide valuable information for the further development and improvement of prophylactic HBV immunoglobulins.

Comparison of complete sequences of hepatitis B virus genotype C between inactive carriers and hepatocellular carcinoma patients before and after seroconversion

“…Clinical and virological characteristics of HCC patients with HBV genotype C in HCC patients, and all of the core deletions around the center of the core region in HCC patients. These pre-S and core deletion sites including B-and T-cell epitopes [21][22][23][24][25] were consistent with those reported in previous papers describing patients infected with pre-S and core deletion mutants. 7,[26][27][28] Previous studies have shown that pre-S deletion mutants tend to accumulate at the later stage of HBV infection 3,4,29,30 and have demonstrated a marked decrease in the synthesis and secretion of small surface protein leading to retention of envelope protein and viral particles within hepatocytes, resulting in the ground-glass appearance of hepatocytes.…”

PreS deletion mutations of hepatitis B virus in chronically infected patients with simultaneous seropositivity for hepatitis‐B surface antigen and anti‐HBS antibodies

“…The S protein contains 226 amino acids (aa) in length, with the M and L proteins being assembled by aminoterminal extension of 55 aa of the preS2 domain and 108-119 aa (depending on strains) of the preS1 domain, respectively [Locarnini et al, 2003]. The preS region is vital to interaction with immune responses due to the Band T-cell epitopes in this region [Kuroki et al, 1990;Maeng et al, 2000;Park et al, 2000;Chen et al, 2006]. Meanwhile, the same region contains several functional and structural sites that are essential to the viral life cycle, such as the hepatocyte binding region, the CCAAT box, and the S promoter sites [Cabrerizo et al, 2000[Cabrerizo et al, , 2002Chen et al, 2006].…”

Fine mapping of hepatitis B virus pre‐S deletion and its association with hepatocellular carcinoma

“…The pre-S region also plays an essential role in the interaction with the immune responses as they contain both B and T-cell epitopes ( Fig. 1) (19)(20)(21)(22)(23)(24)(25). Recent studies suggested that HBV pre-S deletions are associated with the development of HCC (7,10,(26)(27)(28).…”