Hepatitis A Vaccine Development in Japan

In Japan, hepatitis A virus (HAV) infection has been infrequent for many years, with the result that a significant number of individuals have no immunity to the virus. Almost all people younger than 35 years of age have no antibody and are susceptible to HAV. This may cause large outbreaks if prophylactic measures are not available. In our efforts to develop a vaccine, a genotype 3B strain of HAV (KRM003) from a Japanese patient was isolated, adapted, and propagated in an African green monkey kidney (AGMK) cell culture. Formalin-inactivated virus preparation from this culture was highly immunogenic and protective in Saguinus monkeys. Employing a cloned virus (KRM003C3) as the seed, and an established AGMK cell line (GL37) as the cell substrate, we then developed for human use a new lyophilized inactivated vaccine containing neither adjuvant nor preservative. The pilot vaccine lots have been evaluated in 1869 volunteers as clinically tolerable and highly immunogenic.