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Achieving Immunity in Hepatitis B Vaccine Nonresponders

Three double doses of the combined hepatitis A/B vaccine provided protective HBV immunity in 95% of hepatitis B vaccine nonresponders.

Approximately 5% of hepatitis B vaccine recipients do not generate antibodies to hepatitis B surface antigen (anti-HBs) at a protective level (10 mIU/mL). Several strategies to induce protective immunity among these "nonresponders" have been tested, with varying success. Investigators in Sweden recently assessed the effectiveness of the combined hepatitis A/B vaccine in 64 adults — 44 nonresponders who had not developed protective anti-HBs levels after 4 intradermal doses of the Engerix-B recombinant hepatitis B vaccine and 20 control participants who were not immune to hepatitis B virus (HBV) or hepatitis A virus (HAV) and had never received the hepatitis B vaccine. All participants received 2 mL of combined hepatitis A/B vaccine at 0, 1, and 6 months; serum samples were obtained before each dose and 1 month after the last two doses.

Among the 44 nonresponders, 26 (59%), 35 (80%), and 42 (95%) showed protective anti-HBs levels after the first, second, and third hepatitis A/B vaccine doses, respectively. All 20 controls attained such immunity (10%, 95%, and 100%, respectively). Thirty-five of the 44 nonresponders (80%) developed anti-HBs titers >100 IU/mL. The two persistent nonresponders were smokers, and both smoking and high body-mass index were associated with lower anti-HBs levels. All 64 participants developed anti-HAV antibodies.

Comment: For hepatitis B vaccine nonresponders who are not immune to HAV, the combined hepatitis A/B vaccine seems to be an effective and well-tolerated approach to generating anti-HBs responses. More study is needed to directly compare this strategy with others (including repeating the hepatitis B vaccine series or using more-potent adjuvants) and to determine what role the hepatitis A immune response plays in inducing the hepatitis B response. As an editorialist notes, we don’t know how effective (or how well tolerated) the combined vaccine would be among persons who are already immune to HAV.

— Daniel J. Diekema, MD, MS

Published in Journal Watch Infectious Diseases July 2, 2008

Citation(s):

Cardell K et al. Excellent response rate to a double dose of the combined hepatitis A and B vaccine in previous nonresponders to hepatitis B vaccine. J Infect Dis 2008 Jun 10; [e-pub ahead of print]. (http://dx.doi.org/10.1086/589722)

Diepolder HM. Can specific heterologous immunity boost hepatitis B vaccine responses? J Infect Dis 2008 Jun 10; [e-pub ahead of print]. (http://dx.doi.org/10.1086/589721)