Safety profile and immunogenicity of an inactivated vaccine derived from an attenuated strain of hepatitis A.

To determine the safety and immunogenicity of an inactivated hepatitis A vaccine, 56 healthy adult volunteers were randomly assigned to receive an intramuscular injection of 6.3, 12.5 or 25 ng of inactivated hepatitis A vaccine or placebo at 0, 2 or 4, and 24 weeks. Adverse reactions occurred with similar frequency in vaccine and placebo recipients and consisted primarily of pain or tenderness at the injection site. By 4 weeks after a single 6.3, 12.5 or 25 ng injection, seven, nine and ten out of ten vaccinees, respectively, had antibody detectable by a HAV AB assay modified to increase its sensitivity tenfold. All vaccinees had antibodies detectable by this assay within 2 weeks of their second inoculation. Geometric mean antibody levels increased with higher doses of vaccine (p = 0.05). Neutralizing antibody was detected within 4 weeks of a single inoculation in all vaccinees. Neutralizing antibody was detected after the third inoculation at dilutions of greater than or equal to 1:2048 in all 12.5 and 25 ng vaccinees. All 19 vaccinees tested at 24 months still had HAV antibodies detectable by a modified HAV AB assay. This inactivated hepatitis A vaccine appears to be well tolerated and immunogenic at doses of 6.3-25 ng. The choice of dose and vaccination schedule may depend on the rapidity with which seroconversion is desired.