Volume 22-01
1 January 1996

[Table of Contents]

National Advisory Committee on Immunization (NACI)*

SUPPLEMENTARY STATEMENT ON HEPATITIS A PREVENTION

In a recent statement on the prevention of infections caused by hepatitis A virus (HAV), NACI (1) described the usual indications for use of immune serum globulin (IG) and the newly available inactivated hepatitis A vaccine (HAVRIXTM, SmithKline Beecham). Subsequently, a more potent vaccine formulation was licensed, permitting a single dose primary immunization of adults. This supplementary statement addresses this development and comments on vaccine use in children.

New Vaccine Formulation for Adults
When inactivated hepatitis A vaccine (HAVRIXTM, SmithKline Beecham) was first licensed in Canada, the formulation for adults contained 720 enzyme-linked immunosorbent assay (ELISA) units (ELU) of viral antigen in 1.0 mL, to be administered as a three-dose series (at 0, 1 and 6 to 12 months) (1). The new formulation contains 1,440 ELU per 1.0 mL dose, to be administered as a single primary dose. In studies of healthy adults (2), 88% had serum antibody against HAV measurable by ELISA 2 weeks after receiving a 1,440 ELU primary dose and 99% seroconverted after 4 weeks. Virus neutralizing antibody, a better indicator of protection, was present in 94% 4 weeks post-immunization (2) but is not consistently present until that time. Current data for HAVRIXTM (2) indicate that antibodies will persist for at least 1 year in most individuals following the single primary dose. A booster dose may be administered at any time between 6 and 12 months after the primary dose, to induce long-term persistence. A satisfactory booster dose response can be achieved using a dose of either 720 or 1,440 ELU. Kinetic models of antibody decline suggest that protective levels of anti-HAV could persist for at least 20 years (2).

The two formulations differ little in the frequency of adverse reactions. Local adverse reactions are most likely to result from the alum adjuvant, the concentration of which does not differ between the 720 and 1,440 ELU formulations. Both are preserved with 2-phenoxyethanol and contain the same concentrations of trace ingredients. In pre-licensure studies (2), injection site soreness was reported after half the vaccinations with 1,440 ELU but was usually mild. Induration, redness or swelling are reported after 4% to 7% of vaccinations. Systemic adverse events were similar for the HAVRIXTM formulations with headache being the most frequently reported symptom (about 14% of vaccinations), followed by malaise (7%).

HAVRIXTM 1,440 can be given concurrently with IG, at separate injection sites, for persons needing rapid protection, i.e., whose exposure will begin within 4 weeks of vaccination. HAVRIXTM 1,440 is not recommended for children.

The particular advantages of the new formulations are 1) a simplified, one-dose primary immunization course, 2) a shorter interval between vaccination and induction of protective antibody responses against HAV in most individuals (about 4 weeks), and 3) reduced cost of primary immunization. The new formulation will be more convenient for travellers needing protection prior to entering HAV-endemic areas and will be better suited for use in controlling outbreaks (an application that is still considered investigational). Vaccine use in outbreaks should only be considered after discussion with public health officials.

Vaccine Use in Children
HAVRIXTM is not yet licensed for children in Canada and no specific pediatric formulation is available. In the United States, licensure includes use in children 2 to 18 years of age, for whom a dosage of 360 ELU is recommended, in a schedule of 0, 1 and 6 to 12 months (3). The U.S. licensure provisions reflect a more up-to-date application than was available in Canada. It is likely that licensure in Canada will be updated to coincide with that in the U.S. In an(1) should be offered it if they fall into one of the categories for which it is recommended. The appropriate dose (360 ELU) is more readily achieved by splitting a vial containing 720 ELU in 1.0 mL than one with 1,440 ELU in 0.1 mL.

In general, children respond well to HAV vaccine, with over 90% developing antibody within 4 weeks of receiving the first dose (2, 6). Use of a larger initial dose (720 ELU) to elicit protection in children with one vaccination is being evaluated but no recommendation can be made at this time.

Limited data are available on vaccine use in children younger than 24 months (4) but they raise no special concerns regarding vaccine safety. Infants with maternally-derived antibody to HAV may have blunted responses to HAV vaccine, analogous to adults given IG and vaccine concurrently (5) . The dosage for children of all ages is 360 ELU, in a schedule of 0, 1 and 6 to 12 months.

References

1. National Advisory Committee on Immunization. Statement on the prevention of hepatitis A infections. CCDR 1994;20: 133-36,139-43.

2. Clemens R, Safary A, Hepburn A et al. Clinical experience with an inactivated hepatitis A vaccine. J Infect Dis 1995;171(Suppl. 1):S44-S49.

3. CDC. Hepatitis A vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 1995. In press.

4. Horing YC, Chang MH, Lee CY et al. Safety and immunogenicity of hepatitis A vaccine in healthy children. Pediatr Infect Dis J 1993;12:359-62.

5. Green MS, Cohen D, Lerman Y et al. Depression of the immune response to an inactivated hepatitis A vaccine administered concomitantly with immune globulin. J Infect Dis 1993;168:740-43.

6. Balcarek KB, Bagley MR, Pass RF et al. Safety and immunogenicity of an inactivated hepatitis A vaccine in pre-school children. J Infect Dis 1995;171(Suppl. 1):S70-S72.

* Members: Dr. D. Scheifele (Chairman); Dr. J. Spika (Executive Secretary); N. Armstrong (Advisory Committee Secretariat Officer); Dr. F. Aoki; Dr. S. Corber; Dr. P. Déry, Dr. P. DeWals; Dr. S. Halperin; Dr. B. Law; Dr. M. Naus; Dr. Y. Robert; Dr. B. Ward.

Liaison Members: Dr. D. Carpenter (ND); Dr. A. Carter (CMA); Dr. T. Freeman (CFPC); Dr. S. Hadler (CDC); Dr. V. Marchessault (CPS); Dr. H. Robinson (MSB); Dr. J. Waters (ACE).

Ex-Officio Members: Dr. P. Duclos (LCDC); Dr. L. Palkonyay (Drugs Directorate); and Dr. M. Smith (Drugs Directorate).

[Previous] [Table of Contents] [Next]