Achieving Immunity in Hepatitis B Vaccine Nonresponders

Summary and Comment |
July 2, 2008

Achieving Immunity in Hepatitis B Vaccine Nonresponders

  1. Daniel J. Diekema, MD, MS

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

  1. Daniel J. Diekema, MD, MS

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.


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.


Reader Comments (3)

Andrew Quek Other Healthcare Professional, Other, Healthcare MNC

Hi, I am 25-29 yrs old healthy Asian male (Liver panel tests showed no pathologies) who received 3 doses of A/B Hep vaccinations doses. The Hep A immunity was achieved.

However the Hep B was very low at <3.1mIU/ml.

A Hep B booster was administered but only return a 3.6mIU/ml.

A fifth shot for Hep B was adminstered but return again a <3.1mIU/ml.

Are there any other studies that might have bring light to a minute group of non-responders? Because I am interested in finding out about persistent non-responders to Hep B vaccines. The results were too puzzling for my family doctor to make sense of.

Kindest regards,
Andrew Q.

subrata samanta, MD, MRCP Physician, Family Medicine/General Practice, private medical centre

I would like to know the strategy for vaccination to hep-B non-responders who are immune to hep-A (pos anti-HAV). Does double dose of Engerix-B help?

Kathy S. Carson

If the index is 1.00=10mIU/mL and I have 8.09 would I be considered to have immunity?

Competing interests: None declared

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Daniel J. Diekema, MD, D(ABMM)

Contributing Editor 2010 – 2014, Associate Editor 2006-2009