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Immunogenicity Study of an Inactivated Hepatitis A Vaccine in Infants and Young Children

Phase 4
Completed
Conditions
Hepatitis A
Interventions
Biological: hepatitis A vaccine
Registration Number
NCT00139113
Lead Sponsor
Centers for Disease Control and Prevention
Brief Summary

Infants born to immune mothers and therefore having passively-transferred maternal antibody (PMA) to hepatitis A virus (HAV) have a blunted immune response to hepatitis A vaccine. We compared the immunogenicity of hepatitis A vaccine among infants with and without PMA, vaccinated on different schedules. We found that when vaccination is begun at or after 12 months of age, there was no difference in the immune response to the vaccine between infants born to immune vs. susceptible mothers.

Detailed Description

Background: Infants with passively-transferred maternal antibody (PMA) to hepatitis A virus (HAV) have a blunted immune response to hepatitis A vaccine. We compared the immunogenicity of hepatitis A vaccine among infants with and without PMA, vaccinated on different schedules.

Methods: Infants were randomized to one of three groups, each receiving two doses of 720 EL.U. of hepatitis A vaccine (HAVRIX, Glaxo SmithKline) according to the following schedules: Group 1 at ages 6 and 12 months; Group 2 at ages 12 and 18 months; Group 3 at ages 15 and 21 months. We determined antibody to HAV (anti-HAV) status of mothers at the time of delivery, and measured infants' anti-HAV concentrations at the time of the first vaccine dose (baseline), and at 1, 7 and 12 months thereafter. Anti-HAV concentrations \> 33 milli-International Units/milliliter (mIU/mL) were considered protective. We monitored adverse reactions using diary cards and chart reviews.

Results: A total of 239 infants were enrolled, including 134 born to anti-HAV negative mothers (Groups 1N, 2N, 3N) and 105 born to anti-HAV positive mothers (Groups 1P, 2P, 3P).

At month 12, 6 months after the second vaccine dose, the difference in GMC between Groups 1P and 1N was the only statistically significant difference within groups (p\<0.05). There were no statistically significant differences in GMC among groups of infants born to anti-HAV negative mothers ("N" groups), but the difference between Group 1P and Group 3P infants was significant (p \< 0.05). No serious adverse reactions related to vaccination were detected.

Conclusions: Hepatitis A vaccine is immunogenic among infants born to anti-HAV negative mothers, and among those born to anti-HAV positive mothers and vaccinated beginning as young as 12 months old. The persistence of PMA for at least six months among the majority of infants born to anti-HAV positive mothers results in lower seroconversion rates and GMC's.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
248
Inclusion Criteria

term infant with normal growth and development, considered to be healthy at age 6 months; written informed consent by parent/guardian -

Exclusion Criteria

received or expected to receive immune globulin or blood/blood products while enrolled; received or expected to receive immunosuppressive therapy within 30 days of vaccination or has immune deficiency; currently enrolled in another vaccine trial; progressive or unstable neurological disorder

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
HAVRIX age 6, 12 mos; mom antibody neghepatitis A vaccineHAVRIX administered to infants born to anti-HAV negative mothers at ages 6 and 12 months
HAVRIX ages 15,21 mos; mom antibody +hepatitis A vaccineHAVRIX administered to infants born to anti-HAV positive mothers at ages 15 and 21 months
HAVRIX ages 15,21 mos; mom antibody -hepatitis A vaccineHAVRIX administered to infants born to anti-HAV negative mothers at ages 15 and 21 months
HAVRIX 6 and 12 mos; mother antibody poshepatitis A vaccineHAVRIX administered to infants born to anti-HAV positive mothers at ages 6 and 12 months
HAVRIX ages 12, 15 mos; mom antibody +hepatitis A vaccineHAVRIX administered to infants born to anti-HAV positive mothers at ages 12 and 15 months
HAVRIX ages 12, 15 mos; mom antibody-hepatitis A vaccineHAVRIX administered to infants born to anti-HAV negative mothers at ages 12 and 15 months
Primary Outcome Measures
NameTimeMethod
concentration of antibody to hepatitis A virusbaseline and 1, 7, and 12 months post vax

Sera obtained at time of first hepatitis A vaccine dose (baseline) and 1, 7, and 12 months thereafter

Secondary Outcome Measures
NameTimeMethod
reported side effects and adverse eventsday of vaccination and 3 days thereafter

at time of each vaccine dose, parent was given a diary card on which to record systemic and injection site signs and symptoms observed on day of vaccination and subsequent 3 days.

antibodies to routine childhood vaccinationsage 13 months

in a sample of study subjects from each group, blood drawn at age 13 months was tested for response to routine vaccinations.

Trial Locations

Locations (2)

Anchorage Neighborhood Health Center

🇺🇸

Anchorage, Alaska, United States

Alaska Native Medical Center

🇺🇸

Anchorage, Alaska, United States

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