Live attenuated vaccine for hepatitis A

The successful development of hepatitis B vaccines has stimulated interest in the active immunoprophylaxis of type A hepatitis. The development of hepatitis A vaccines has been simplified by the ability to propagate HAV in tissue culture systems and the availability of animal model systems, including the chimpanzee and certain species of marmosets in which to evaluate safety and efficacy of candidate vaccines. Both inactivated and live, attenuated hepatitis A vaccines are possible, but the limited replicative ability of HAV in tissue culture makes the former impractical at present. However, HAV appears to be rapidly attenuated by serial passage in tissue culture and such attenuated strains are candidates for a live, attenuated vaccine similar to the Sabin polio vaccine. The HM-175 strain of HAV, recovered from the stool of a patient with type A hepatitis in Melbourne, Australia, was isolated directly in primary African green monkey kidney (AGMK), a cell substrate suitable for vaccine development. This strain has been serially passaged over 20 times in AGMK. The parent strain (stool extract) and virus at tissue culture passages 10 and 20 were evaluated for infectivity and virulence in seronegative chimpanzees. The parent strain produced evidence of liver damage (elevated liver enzymes) at all dilutions of infectious virus tested. In contrast, tissue culture-passaged virus was fully infectious for chimpanzees, but did not produce biochemical evidence of hepatitis. Similarly, hepatitis A viral antigen could not be detected in liver biopsies and little or no viral antigen could be detected in acute phase stool samples.(ABSTRACT TRUNCATED AT 250 WORDS)