SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF AN INACTIVATED HEPATITIS-A VACCINE - EFFECTS OF SINGLE AND BOOSTER INJECTIONS, AND COMPARISON TO ADMINISTRATION OF IMMUNE GLOBULIN

Hepatitis A virus (HAV) infection in adults is often symptomatic and disabling. The present article summarizes our experience with phase 2 studies of an inactivated hepatitis A virus vaccine. Pre- and post-exposure prophylaxis with immune globulin (IG) is only effective for 4-6 months. We compared the safety, tolerability, and immunogenicity of a single i.m. injection of IG with single and booster doses of an inactivated hepatitis A virus vaccine (iHAV) in adults. A total of 75 healthy volunteers (aged 18-50 years) were evaluated in two separate studies. The first included 15 volunteers who received 25 units iHAV i.m. at 0 and 24 weeks. The second, a randomly controlled study, consisted of three groups receiving 25 units iHAV i.m. at 0, 1, and 6 months, or at 0, 2, and 6 months, or 0.06 ml/kg IG i.m. given once. Anti-HAV seroconversion was measured by radioimmunoassay (RIA). After IG injection, anti-HAV seroconversion occurred in 100% of recipients at week 1, declining to 10% at week 12, and 0% by week 20. In contrast, after a single 25-unit dose, RIA seropositivity in iHAV vaccinees was 73% by week 2, reaching 100% by week 5, and persisted in all up to week 24, at which time anti-HAV geometric mean titers (GMT) were 2-fold higher than those seen at week 1 after IG. Administration of a booster dose given 1 or 2 months after primary immunization did not significantly improve the quantitative anti-HAV response at 6 months as compared to the effect of the primary dose. In vaccinees who received only two doses, at 0 and 6 months, post-booster anti-HAV titers rose within 4 weeks after the 6 months dose to almost 70-fold higher than the peak GMT seen one week after IG, and almost 40-fold higher than the GMT at 12 weeks after IG. The iHAV was well tolerated, with no serious adverse experiences observed. In conclusion, active vaccination with a single iHAV dose may eventually replace IG for pre-exposure prophylaxis. Furthermore, the two-dose (0, 6 months) 25-unit iHAV regimen provides longer lasting anti-HAV titers, greatly exceeding those afforded by IG.