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Comparison of Higher-Dose Intradermal Hepatitis B Vaccination to Standard Intramuscular Vaccination of Healthcare Workers

  • Elizabeth A. Henderson (a1) (a2), Thomas J. Louie (a1) (a3) (a4), Karam Ramotar (a1) (a4), Donna Ledgerwood (a1), Karen Myrthu Hope (a1) and Agnes Kennedy (a1)...



To compare the immunogenicity of hepatitis B vaccine administered via intradermal (ID) versus intramuscular (IM) route.


Subjects chose either to specify the route of immunization or to undergo random allocation to vaccination by the ID (0.15 mL) or the IM (1.0 mL) route. Yeast-derived recombinant hepatitis B vaccine was given at 0, 30, and 180 days. Hepatitis B surface antibody (HBsAb) and hepatitis B core antibody (HBcAb) were measured by microparticle enzyme immunoassay.


763 subjects were enrolled. Baseline screening identified 65 subjects (8%) who were positive for HBsAb or HBcAb. Vaccination was completed by 590 (85%) of 698 enrollees (370 ID, 220 IM). Seroconversion rates (geometric mean titers [GMT]>0 IU/mL HBsAb) for those vaccinated ID were 99% and 96% for screening at 9 months and 1 year post-vaccination, respectively; subjects vaccinated intramuscularly had similar rates of 95% and 96%. Seropositivity rates (GMT ≥ 10 IU/mL HBsAb) showed a similar pattern, with 95%, 92%, and 73% at 9 months and 1 and 2 years, respectively, for those vaccinated ID, and 94%, 93%, and 81% for those having IM vaccination. GMT for HBsAb was significantly higher for individuals vaccinated IM than for those vaccinated ID (P<.0001). The GMT ratio for the IM and ID routes decreased over time, being 9.3 at 9 months, 7.8 at 1 year, and 5.9 at 2 years. An unanticipated side effect of intradermal vaccination was skin discoloration at injection sites, which persisted for at least 2 years postvaccination. Two thirds (112/166) of respondents reported that they would have selected the ID route despite the discoloration.


Higher-dose ID vaccination (3 vs 1 μg per injection) uses one sixth of the dose required for standard IM vaccination. It is a cost-effective way to vaccinate populations against hepatitis B virus, but the long-term efficacy of the ID route must still be investigated.


Corresponding author

Infection Prevention and Control, Peter Lougheed Center of the Calgary General Hospital, 3500—26 Ave NE, Calgary, Alberta T1Y6J4, Canada


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Comparison of Higher-Dose Intradermal Hepatitis B Vaccination to Standard Intramuscular Vaccination of Healthcare Workers

  • Elizabeth A. Henderson (a1) (a2), Thomas J. Louie (a1) (a3) (a4), Karam Ramotar (a1) (a4), Donna Ledgerwood (a1), Karen Myrthu Hope (a1) and Agnes Kennedy (a1)...


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