Sl. Block et al., SAFETY, TOLERABILITY AND IMMUNOGENICITY OF A FORMALIN-INACTIVATED HEPATITIS-A VACCINE (VAQTA(R)) IN RURAL KENTUCKY CHILDREN, The Pediatric infectious disease journal, 12(12), 1993, pp. 976-980
This study evaluated the immunogenicity and safety/tolerability profil
e of an investigational formalin-inactivated hepatitis A virus vaccine
(VAQTA(R); Merck Research Laboratories) in 150 seronegative healthy c
hildren, 4 to 12 years old. The vaccine was derived from virus grown i
n infected MRC-5 cells in either roller bottles or Nunc cell factories
(Nunc, Denmark). Subjects were vaccinated intramuscularly in a two do
se 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 fr
om 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 fir
st 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 7
9 and 7059 to 29 609 mIU/ml, respectively. The 12- and 25-unit dose le
vels 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 G
roup 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 rea
ctions at the injection site occurred in about one-half of all vaccine
es. Non-injection site reactions, chiefly headache (3 to 6%, nonsignif
icant), were minor and uncommon, and often reflected intercurrent back
ground conditions. Laboratory abnormalities were rare, mild and clinic
ally insignificant. The three lots of VAQTA(R) tested were well-tolera
ted in this pediatric population. The evidence of immune memory and th
e high titers achieved after a single booster dose suggest long lastin
g immunity with the two dose regimen. The role of this vaccine in post
exposure prophylaxis and in routine childhood immunizations warrants f
urther investigation.