SAFETY, TOLERABILITY AND IMMUNOGENICITY OF A FORMALIN-INACTIVATED HEPATITIS-A VACCINE (VAQTA(R)) IN RURAL KENTUCKY CHILDREN

This study evaluated the immunogenicity and safety/tolerability profile of an investigational formalin-inactivated hepatitis A virus vaccine (VAQTA(R); Merck Research Laboratories) in 150 seronegative healthy children, 4 to 12 years old. The vaccine was derived from virus grown in infected MRC-5 cells in either roller bottles or Nunc cell factories (Nunc, Denmark). Subjects were vaccinated intramuscularly in a two dose regimen initially and at 24 weeks: Group A (n = 50) with a 12-unit dose from a roller bottle lot; Group B (n = 50) with a 25-unit dose from another roller bottle lot; and Group C (n = 50) with a 25-unit dose from a Nunc cell lot. Sera for anti-hepatitis A virus antibodies were drawn 3 weeks before vaccination and 4, 24 and 28 weeks after the first dose. Seroconversion from <10 mIU/ml to greater-than-or-equal-to 10 mIU/ml by modified HAVAB(R) (Abbott Laboratories) was observed in 99% of subjects at week 4 and persisted in 100% of subjects at week 28 (4 weeks after the second dose). The ranges of geometric mean titers of anti-HAV for all subjects at weeks 4, 24 and 28 were 31 to 49, 51 to 79 and 7059 to 29 609 mIU/ml, respectively. The 12- and 25-unit dose levels of roller bottle yielded similar geometric mean titers. The rise in geometric mean titers after the booster dose was >120-fold and was highest in the recipients of the 25-unit Nunc cell lot (P < 0.05 for Group C vs. B). Neutralizing antibody was detectable in 93% (81 of 87) of the subjects tested at Week 4 in Groups A and C. Mild transient reactions at the injection site occurred in about one-half of all vaccinees. Non-injection site reactions, chiefly headache (3 to 6%, nonsignificant), were minor and uncommon, and often reflected intercurrent background conditions. Laboratory abnormalities were rare, mild and clinically insignificant. The three lots of VAQTA(R) tested were well-tolerated in this pediatric population. The evidence of immune memory and the high titers achieved after a single booster dose suggest long lasting immunity with the two dose regimen. The role of this vaccine in postexposure prophylaxis and in routine childhood immunizations warrants further investigation.