Immunogenicity and safety of a pediatric dose of a virosome-adjuvanted hepatitis A vaccine: a controlled trial in children aged 1-16 years.
BACKGROUND
The availability of pediatric formulations of hepatitis A virus (HAV) vaccines would facilitate the introduction of universal mass vaccination against HAV. The objective of this study was to compare a pediatric dose (0.25 mL) of Epaxal, a virosomal, aluminum-free HAV vaccine, to 0.5 mL standard dose, and to alum-adsorbed HAV vaccine.


METHODS
Subjects aged 1-16 years, stratified for age, were randomized (2:2:1) into group A (0.25 mL Epaxal), group B (0.5 mL Epaxal), or group C (Havrix Junior). Vaccines were administered at months 0, 6. Seroprotection rates (>or=10 mIU/mL anti-HAV antibodies) were assessed for noninferiority, defined as lower limit of 1-sided 97.5% CI >-10%. Incidence of local solicited adverse events and unsolicited adverse events were recorded.


RESULTS
Mean age of 308 enrolled subjects was 8.9 years (range, 1.0-17.0 years). All 3 vaccines were highly immunogenic. Noninferiority of group A versus group B and group C with regard to seroprotection was demonstrated after both vaccine doses for the entire study group and for all age subgroups (11-23 months, 2-4, 5-7, 8-10, 11-13, 14-16 years). One month after first vaccination, geometric mean antibody concentrations were 69.0, 83.5, and 50.5 mIU/mL for the 3 groups, respectively (A versus B, P = 0.0208; A versus C, P = 0.0015). Local injection site pain occurred more frequently in group C than in groups A and B. No subjects withdrew from study or reported any vaccine-related serious adverse event.


CONCLUSIONS
In children aged 1-16 years, 0.25 mL dose of Epaxal is as immunogenic as standard 0.5 mL dose and Havrix Junior. The aluminum-free vaccine compares favorably to comparator vaccine regarding local reactogenicity.
Van Der Wielen
Marie
M
University of Antwerp, Antwerp, Belgium.
Vertruyen
André
A
Froesner
G
G
Ibáñez
Rubén
R
Hunt
Marjory
M
Herzog
Christian
C
Van Damme
Pierre
P
D000293:Adolescent; D000914:Antibodies, Viral / Q000097:blood; D002648:Child; D002675:Child, Preschool; D004890:Erythema / Q000139:chemically induced; D005260:Female; D022362:Hepatitis A Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D006801:Humans; D007117:Immunization, Secondary; D007223:Infant; D007273:Injections, Intramuscular; D008297:Male; D010146:Pain / Q000139:chemically induced; D016896:Treatment Outcome; D022721:Vaccines, Virosome / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
D000914:Antibodies, Viral; D022362:Hepatitis A Vaccines; D022721:Vaccines, Virosome