Serological approaches to distinguish immune response to hepatitis A vaccine and natural infection

Currently, the immune status of an individual exposed to hepatitis A virus (HAV) is determined by assays which measure antibodies against the capsid proteins. These assays indicate exposure to the viral capsid that could result from either infection or from vaccination. Recent data indicate that proteins from the non-structural genome region of the virus (P2 or P3), which are only produced during active virus replication, generate antibodies after clinical disease. A sub-genomic cDNA segment of HAV corresponding to the P2 region was used for in vitro transcription-translation followed by immune precipitation of the translated products under non-denaturing conditions. Serial serum specimens from experimentally infected chimpanzees and humans naturally infected with hepatitis A verified the development of antibodies to P2 proteins following infection. A serosurvey of individuals positive for antibodies to the HAV capsid (HAV AB assay, Abbott Laboratories) revealed that 50-60% of children and 16-32% of adults had no detectable antibodies to the P2 antigen by immune precipitation. These results may reflect subclinical infections resulting in a lower level of antibodies against the non-structural antigens or may represent a greater sensitivity of the competitive assay (HAV AB) used to detect capsid antibodies compared to the immunoprecipitation assay used to detect non-structural antigens.