Immunoprecipitation and Virus Neutralization Assays Demonstrate Qualitative Differences between Protective Antibody Responses to Inactivated Hepatitis A Vaccine and Passive Immunization with Immune Globulin

Abstract

Antibodies to hepatitis A virus (anti-HAV) were measured in children from two separate vaccine trials (n = 70) 4 weeks after a dose of inactivated hepatitis A vaccine (VAQTA). The geometric mean titers (GMTs) of anti-HAV were 49.3 and 45.2 mIU/mL by immunoassay, while reciprocal GMTs of neutralizing anti-HAV were 6.5 and 15.0 by an 80% radioimmunofocus inhibition test (RIFIT) and 55.6 and 92.0 by antigen reduction assay (HAVARNA). The GMT of antibody detected by radioimmunoprecipitation (RIPA) was > or =401. These data establish serologic correlates of protection against disease and show that RIPA is most sensitive for detection of early vaccine-induced antibody. Sera collected from adults (n = 20) 7 days after administration of immune globulin contained similar antibody levels by immunoassay (45.1 mIU/mL) and slightly higher GMTs of neutralizing antibody (27.5 by RIFIT and 146 by HAVARNA) but negligible precipitating antibody (GMT, 5.6). These results are best explained by differences in the affinity of antibodies for virus following active versus passive immunization.