IMMUNE-RESPONSE TO SYNTHETIC PEPTIDES OF HEPATITIS-DELTA ANTIGEN

Hepatitis delta antigen (HDAg) is the only viral protein known to be e xpressed during hepatitis delta virus (HDV) infection. Detection of an tibody to HDAg (anti-HD) is the usual method for diagnosis of HDV infe ction since viremia lasts only a few weeks. In an effort to identify t he major epitopes recognized by humans during natural infection, four oligopeptides including residues 2 to 17 (SP1), 155 to 172 (SP2), 168 to 182 (SP3), and 189 to 211 (SP4) of the HDAg molecule were synthesiz ed and probed by enzyme-linked immunosorbent assay with a panel of 80 serum specimens from 45 patients suffering from either HDV-hepatitis B virus coinfections (n = 17) or HDV superinfections (n = 28). Sera fro m infected patients recognized these relatively short peptides. Peptid e SP2 was the most antigenic; 71% of serum specimens reacted. Antibody to SP2 was also the commonest in sera taken early in the course of th e disease. Peptide SP2 corresponds to one of the two regions which is highly conserved between different isolates. Among the 63 serum specim ens which scored anti-HD positive by a commercial assay, all but 3 rea cted to at least one of the peptides (95% agreement). Peptide assays a ppeared to be significantly more sensitive than the commercial assay w ith native HDAg early in the course of HDV infection since 14 of 17 (8 2%) serum specimens which scored anti-HD negative in the commercial as say reacted to one or more peptides. All serum specimens giving one or more positive results with the various peptides were confirmed as bei ng HDV positive by an inhibition assay with free peptide in solution. The immune response to HDAg peptides varied greatly between individual s. No specific reactivity profile could be assigned to those with eith er HDV-hepatitis B virus coinfections or HDV superinfections. Overall, HDAg peptides appeared to be convenient reagents in addition to nativ e antigen for the development of new and improved diagnostic tests for HDV infection.