VAQTA PAEDIATRIC Suspension for injection Ref.[50245] Active ingredients: Hepatitis A, inactivated vaccine

Pharmacotherapeutic group: viral vaccines, hepatitis A, inactivated, whole virus
ATC code: J07BC02

VAQTA Paediatric is derived from hepatitis A virus that has been cultured in human MRC-5 diploid fibroblasts. It contains inactivated virus of a strain which was originally derived by further serial passage of a proven attenuated strain. The virus is grown, harvested, highly purified, formalin inactivated, and then adsorbed onto amorphous aluminium hydroxyphosphate sulfate.

Mechanism of action

Hepatitis A vaccine elicits circulating neutralising antibodies to Hepatitis A virus sufficient to confer protection against the virus.

Clinical efficacy and safety

Efficacy of VAQTA Paediatric: The Monroe Clinical Study

Clinical studies showed that the seroconversion rate in children approximately 12 months of age was 96% within 6 weeks after the recommended primary dose and that the seroconversion rate was 97% in children (≥2 years of age) and adolescents within 4 weeks after the recommended primary dose. The onset of seroconversion following a single dose of VAQTA Paediatric was shown to parallel the onset of protection against clinical hepatitis A disease. Protective efficacy has been demonstrated after a single dose of VAQTA Paediatric in 1,037 children and adolescents 2 to 16 years of age in a US community with recurrent outbreaks of hepatitis A (The Monroe Efficacy Study). Seroconversion was achieved in more than 99% of vaccine recipients within 4 weeks of the vaccination. The pre-exposure protective efficacy of a single dose of VAQTA Paediatric was observed to be 100% beginning 2 weeks after vaccination. A booster dose was administered to most vaccinees 6, 12, or 18 months after the primary dose. The effectiveness of VAQTA Paediatric for use in this community has been demonstrated by the fact that after 9 years, since the trial ended, there has been no case of hepatitis A disease in any vaccinee.

Persistence of immunologic memory was demonstrated with an anamnestic antibody response to a booster dose given 6 to 18 months after the primary dose in children (≥2 years of age) and adolescents. To date, no cases of clinically confirmed hepatitis A disease ≥50 days after vaccination have occurred in these vaccinees from the Monroe Efficacy Study monitored for up to 9 years.

Immunogenicity studies in children 12 through 23 months of age

In three combined clinical studies that assessed immunogenicity, 1,022 initially seronegative subjects received 2 doses of VAQTA Paediatric alone or concomitantly with other vaccines (combined diphtheria toxoid-tetanus toxoid-acellular pertussis and/or Haemophilus influenzae b and/or combined measles-mumps-rubella-varicella and/or combined measles-mumps-rubella and/or varicella and/or pneumococcal 7-valent conjugate vaccine). Seroconversion was achieved in 99.9% of initially seronegative subjects. No significant differences were observed when vaccines were given individually or concomitantly.

Use in children with maternal antibody to hepatitis A

In a concomitant use study, children received VAQTA Paediatric (25 U) at approximately 12 months and approximately 18 months of age with or without other paediatric vaccines. After each dose of VAQTA Paediatric (25 U), the hepatitis A antibody titres were comparable between children who were initially seropositive to hepatitis A and children who were initially seronegative to hepatitis A. These data suggest that maternal antibody to hepatitis A in children approximately 12 months of age does not affect the immune response to VAQTA Paediatric.

Antibody persistence

In studies of healthy children (≥2 years of age) and adolescents who received an initial 25 U dose of VAQTA Paediatric at Day 0 and a subsequent 25 U dose 6 to 18 months later, the hepatitis A antibody response to date has been shown to persist for at least 10 years. The geometric mean titres (GMTs) tend to decline over time. The GMTs declined over the first 5 to 6 years, but appeared to plateau through 10 years.

Data available from long-term studies up to 10 years on the persistence of HAV antibodies after 2 doses of VAQTA in healthy, immunocompetent subjects up to 41 years of age allows prediction that based on mathematical modeling at least 99% of subjects will remain seropositive (≥10 mlU anti-HAV/mL) at least 25 years after vaccination.

Based on this analysis, an additional vaccination following complete primary immunisation with 2 doses appears to be unnecessary. However, decisions regarding additional vaccination should be based on risk-benefit for the individual.

Post-marketing safety study

In a post-marketing safety study, conducted at a large health maintenance organisation in the United States, a total of 12,523 individuals 2 through 17 years of age received 1 or 2 doses of VAQTA Paediatric. Safety was monitored by reviewing medical records that tracked emergency room and outpatient visits, hospitalisations and deaths. There was no serious, vaccine-related, adverse event identified among the 12,523 individuals in this study. There was no nonserious, vaccine-related, adverse event resulting in outpatient visits. There was no vaccine-related, adverse event identified that had not been reported in earlier clinical trials with VAQTA Paediatric.