Detection of antibodies to HAV 3C proteinase in experimentally infected chimpanzees and in naturally infected children.

Commercial assays for the diagnosis of hepatitis A detect antibody to hepatitis A virus (anti-HAV), but they cannot discriminate between antibody resulting from infection and antibody induced by inactivated vaccine. With the licensing and increasing use of inactivated hepatitis A vaccines, there is a need for a test to distinguish between infection and vaccination. Since antibodies to viral non-structural proteins are elicited by infection but not by vaccination with inactivated vaccine, we developed and evaluated a test for such antibodies. The antibody response to the non-structural 3C proteinase (anti-3C) of virus HAV was studied by ELISA in chimpanzees experimentally infected with virulent (wild type) or with attenuated HAV strains and in children who received inactivated HAV vaccine or placebo during a vaccination trial in Nicaragua. Anti-3C was detected in 89% of 18 chimpanzees infected with wild-type HAV strains and 27% of 26 chimpanzees infected with attenuated HAV strains. There was a direct correlation between severity of hepatitis and magnitude of the anti-3C response. In the vaccine trial, anti-3C was detected only in children who were infected with HAV during the study; IgG anti-3C persisted for at least 15 months after infection in one child. Vaccinated and uninfected children remained negative for anti-3C. The anti-3C response can be regarded as an indicator of viral replication. Its detection should be useful for distinguishing between antibody acquired in response to HAV infection and antibody induced by immunization with inactivated vaccine.