Hepatitis A Prevention Through Immunization : Vaccine

by CDC

(Page 7 of 13)

Route of Administration, Vaccination Schedule, and Dosage

The vaccine should be administered intramuscularly into the deltoid muscle. A needle length appropriate for the person's age and size should be used.

VAQTA is licensed in two formulations, which differ according to the person's age. Persons aged 12 months - 18 years should receive 25 U per dose in a 2-dose schedule; persons aged >18 years should receive 50 U per dose in a 2-dose schedule.

HAVRIX is available in two formulations, which differ according to the person's age: for persons aged 12 months - 18 years, 720 EL.U. per dose in a 2-dose schedule; and for persons aged >18 years, 1,440 EL.U. per dose in a 2-dose schedule. A pediatric formulation of 360 EL.U. per dose administered in a 3-dose schedule is no longer available.

TWINRIX is licensed for use in persons aged >18 years. TWINRIX is a combined hepatitis A and hepatitis B vaccine containing 720 EL.U. of hepatitis A antigen (half of the HAVRIX adult dose) and 20 mcg of recombinant hepatitis B surface antigen protein (the same as the ENGERIX-B adult dose). Primary immunization consists of 3 doses, administered on a 0-, 1-, and 6-month schedule, the same schedule as that commonly used for single-antigen hepatitis B vaccine. TWINRIX contains aluminum phosphate and aluminum hydroxide as adjuvant and 2-phenoxyethanol as a preservative. After 3 doses of TWINRIX, antibody responses to both antigens are equivalent to responses seen after the single-antigen vaccines are administered separately on standard schedules.

Vaccine Performance

Detection of Anti-HAV After Vaccination. Concentrations of antibody achieved after passive transfer by IG or active induction by vaccination are 10- to 100-fold lower than those produced after natural infection and can be below the level of detection of certain commercially available diagnostic assays. To measure lower levels of antibody, more sensitive immunoassays were developed for immunogenicity studies that correlate more closely with neutralizing antibody assays. Anti-HAV concentrations are measured in comparison with a World Health Organization reference immunoglobulin reagent and are expressed as milli-International Units per milliliter (mIU/mL). The lower limits of detection have typically been approximately 100 mIU/mL by unmodified commercially available assays and 10 mIU/mL by more sensitive assays. A positive anti-HAV result by a standard assay indicates protection. However, after vaccination, persons who are anti-HAV negative by standard assays might nevertheless have protective levels of antibody.

The absolute lower limit of anti-HAV required to prevent HAV infection has not been defined. In vitro studies using cell-culture-derived virus indicate that low levels of antibody (e.g., < 20 mIU/mL) can be neutralizing. Clinical studies have yielded limited data from which a minimum protective antibody level can be derived because vaccine-induced levels of antibody have been high and few infections have been detected among vaccinated persons. Experimental studies in chimpanzees indicate that low levels of passively transferred antibody (< 10 mIU/mL) obtained from immunized persons do not protect against infection but do prevent clinical hepatitis and virus shedding. To define a protective antibody response, clinical studies conducted with HAVRIX have used levels > 20 mIU/mL, or > 33 mIU/mL in more recent studies, as measured with modified enzyme immunoassays, and studies conducted with VAQTA have used levels > 10 mIU/mL as measured with a modified radioimmunoassay.

Immunogenicity in Adults. All licensed vaccines are highly immunogenic in persons aged >18 years when administered according to the recommended schedules. Protective antibody levels were identified in 94% - 100% of adults 1 month after the first dose. After the second dose, all persons had protective levels of antibody, with high geometric mean antibody concentrations (GMCs).

Limited data are available regarding the timing of the appearance of neutralizing antibody. Among a sample of vaccinated persons, 54% - 62% were positive for neutralizing antibody 14 days after the first dose, and 94% - 100% were positive at 1 month.

Immunogenicity in Children and Adolescents. Both vaccines are highly immunogenic when administered to children and adolescents according to multiple schedules; 97% - 100% of persons aged 2 - 18 years had protective levels of antibody 1 month after receiving the first dose, and 100% had protective levels 1 month after the second dose, with high GMCs. Children with Down syndrome responded to vaccination as well as other children and had similar levels of protective antibody.

Immunogenicity in Infants. Available data indicate that inactivated hepatitis A vaccines are immunogenic in children aged < 2 years who do not have passively acquired maternal antibody. All such infants administered hepatitis A vaccine subsequently had protective antibody levels, with the final GMCs varying depending on the dosage and schedule. Infants with passively acquired maternal antibody had reduced GMCs after vaccination.

IgM Anti-HAV After Vaccination. Hepatitis A vaccination can induce IgM anti-HAV that is detectable by standard assays, particularly if the test is conducted soon after vaccination. IgM anti-HAV has been detected 2 - 3 weeks after administration of one dose of vaccine in 8% - 20% of adults.

Efficacy. The efficacy of HAVRIX was evaluated in a double-blind, controlled, randomized clinical trial conducted in Thailand among approximately 40,000 children aged 1 - 16 years living in villages that had high rates of hepatitis A. After 2 doses of vaccine (360 EL.U. per dose) administered 1 month apart, the efficacy of vaccine in protecting against clinical hepatitis A was 94% (95% confidence interval [CI] = 79% - 99%). A double-blind, placebo-controlled, randomized clinical trial using VAQTA was conducted among approximately 1,000 children aged 2 - 16 years living in a New York community that had a high rate of hepatitis A. The protective efficacy against clinical hepatitis A was 100% (lower bound of the 95% CI = 87%) after administration of 1 dose (25 U) of vaccine.

About the Author

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The Centers for Disease Control and Prevention (CDC) is one of the 13 major operating components of the Department of Health and Human Services (HHS), which is the principal agency in the United States government for protecting the health and safety of all Americans and for providing essential human services, especially for those people who are least able to help themselves.