[Clinical development of a new inactivated hepatitis A vaccine]

An attenuated vaccine against hepatitis A was developed from the GBM strain of the virus, cultured on human diploid MRC5 cells. Each dose contained 160 antigen units, inactivated by formalin and adsorbed onto 0.3 mg aluminum hydroxide, in a volume of 0.5 ml. Intramuscular injection of the vaccine conferred immunity to hepatitis A, with antibody titers greater than those obtained by passive immunization with immunoglobulin. In clinical studies, immunocompromised subjects became immune shortly after the first injection and more than 90% were found to be protected after 14 days (titer above 20 mIU/ml by RIA). All subjects (100%) were protected one month after the first injection. Immunity persisted for at least six months and was strengthened by a booster injection. The antibody titers determined after the first booster injection were consistent with a projected period of protection of ten years. Adverse reactions were mild and occurred within the first few days after vaccination, with the patient usually recovering spontaneously. The most common reaction was mild local pain, usually associated with redness of the skin. A nodule was observed at the injection site in a small number of cases. Mild fever, asthenia, headache, myalgia/arthralgia and gastrointestinal tract disorders were also reported. Reactions were reported less frequently after the booster injection than after the initial dose. The vaccine was as well tolerated by patients seropositive for the hepatitis A virus as by seronegative subjects. Thus, this vaccine can be used for active immunization against hepatitis A in adults and adolescents. It can be administered as primary immunization and as a booster injection.