Prophylaxis Against Hepatitis A Virus Infection

by CDC

(Page 6 of 13)

Immune Globulin

IG is a sterile preparation of concentrated antibodies (immunoglobulins) made from pooled human plasma processed by cold ethanol fractionation. In the United States, only plasma that has tested negative for hepatitis B surface antigen (HBsAg), antibody to human immunodeficiency virus (HIV), and antibody to hepatitis C virus (HCV) is used to produce IG. In addition, FDA requires that the process used to produce IG include a viral inactivation step or that final products test negative for HCV RNA by PCR. Anti-HAV concentrations differ among IG lots, and slightly lower concentrations have been observed over the preceding 30 years, probably because of the decreasing prevalence of previous HAV infection among plasma donors. However, no clinical or epidemiologic evidence of decreased protection has been observed.

IG provides protection against hepatitis A through passive transfer of antibody. Both IG administered intramuscularly (IM) and IG for intravenous administration (IGIV) contain anti-HAV, but IG administered intramuscularly is the product used for the prevention of HAV infection. No transmission of hepatitis B virus (HBV), HIV, HCV, or other viruses has been reported from intramuscular IG. The concentrations of IgG anti-HAV achieved after administration of IG intramuscularly are below the level of detection of the majority of commercially available diagnostic tests. When administered for preexposure prophylaxis, 1 dose of 0.02 mL/kg IM confers protection for < 3 months, and 1 dose of 0.06 mL/kg IM confers protection for 3 - 5 months. When administered within 2 weeks after an exposure to HAV (0.02 mL/kg IM), IG is 80% - 90% effective in preventing hepatitis A. Efficacy is greatest when IG is administered early in the incubation period; when administered later in the incubation period, IG might only attenuate the clinical expression of HAV infection.

IG is available in single-use (2 mL) and multidose (10 mL) vials. Preparations are formulated without a preservative. For administration of IG, an appropriate muscle mass (i.e., the deltoid or gluteal muscle) should be chosen into which a substantial volume can be injected, using a needle length appropriate for the person's age and size. If a gluteal muscle is used, the central region of the buttock should be avoided; only the upper outer quadrant should be used, and the needle should be directed anteriorly to minimize the possibility of injury to the sciatic nerve.

Serious adverse events from IG are rare. Anaphylaxis has been reported after repeated administration to persons with known immunoglobulin A (IgA) deficiency; thus, IG should not be administered to these persons. Pregnancy or lactation is not a contraindication to IG administration.

IG does not interfere with the immune response to oral poliovirus vaccine or yellow fever vaccine, or, in general, to inactivated vaccines. However, IG can interfere with the response to other live, attenuated vaccines (e.g., measles, mumps, and rubella [MMR] vaccine and varicella vaccine) when administered either as individual or combination vaccines. Administration of MMR should be delayed for >3 months and varicella vaccine for >5 months after administration of IG for hepatitis A prophylaxis. IG should not be administered <2 weeks after administration of MMR or <3 weeks after varicella vaccine unless the benefits of IG administration exceed the benefits of vaccination. If IG is administered <2 weeks after administration of MMR or <3 weeks after administration of varicella vaccine, the person should be revaccinated, but not sooner than 3 months after IG administration for MMR or 5 months for varicella vaccine. Hepatitis A Vaccine

Inactivated and attenuated hepatitis A vaccines have been developed and evaluated in human clinical trials and in nonhuman primate models of HAV infection; however, only vaccines made from inactivated HAV have been evaluated for efficacy in controlled clinical trials. The vaccines containing HAV antigen that are currently licensed in the United States are the single-antigen vaccines HAVRIX® (manufactured by GlaxoSmithKline, Rixensart, Belgium) and VAQTA® and the combination vaccine TWINRIX® (containing both HAV and HBV antigens; manufactured by GlaxoSmithKline). All are inactivated vaccines.

Preparation

Inactivated hepatitis A vaccines are prepared by methods similar to those used for inactivated poliovirus vaccine. Cell-culture - adapted virus is propagated in human fibroblasts, purified from cell lysates by ultrafiltration and exclusion gel chromatography or other methods, formalin inactivated, and adsorbed to an aluminum hydroxide adjuvant; 2-phenoxyethanol is used as a preservative for HAVRIX and TWINRIX, and VAQTA is formulated without a preservative. For HAVRIX and TWINRIX, the antigen content of the final aqueous preparation is determined by reactivity in a quantitative immunoassay for HAV antigen, and final vaccine potency (per dose) is expressed as enzyme-linked immunosorbent assay (ELISA) units (EL.U.). For VAQTA, the antigen content is expressed as units (U) of HAV antigen.

Vaccine Storage and Shipment

Hepatitis A vaccine should be stored and shipped at temperatures ranging from 35.6°F - 46.4°F (2°C - 8°C) and should not be frozen. However, the reactogenicity and immunogenicity of HAVRIX after storage at 98.6°F (37°C) for 1 week and the stability profile of VAQTA when stored at this temperature for >12 months do not differ from those of vaccines stored at the recommended temperature.

About the Author

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