June 30, 2008


EIN: What to Do About Hepatitis B Vaccine Non-responders


The Emerging Infections Network (EIN) is a forum for infectious diseases consultants and public health officials to report information on clinical phenomena and epidemiological issues with public health significance. Any diagnostic or therapeutic recommendations and all opinions presented are those of the individual contributor. They do not necessarily represent the views of the EIN, IDSA (EIN's sponsor) or the Centers for Disease Control and Prevention, which funds the EIN. The reader assumes all risks in using this information.


An EIN member’s patient had not developed an immune response after two complete series of hepatitis B vaccine. The member asked for advice on additional measures to generate seroconversion, including the possibility of intradermal administration. The following is a sampling of the responses.

Washington: I have been using the hepatitis B vaccine 0.25 ml intradermally (0, 2, and 4 weeks) in individuals who had not responded to standard dosing. I have had an 80 percent seroconversion rate in these patients. The failures included some dialysis patients but otherwise were unpredictable. Because it is off label, I do a verbal informed consent and give the injections myself. Other than discomfort at the time of injection, the only side effect is erythema at the injection site and occasionally some subtle increased pigmentation after the erythema resolves.

Florida: I gave a 0.125 mL dose of the dialysis formulation of Recombivax (40 mcg/mL) in order to deliver a dose of 5 mcg, as reported previously in the literature. After one dose, the surgeon developed a nice delayed-type hypersensitivity response and had positive titers a month later. The surgeon did, however, complain of itching at the site for several months.

Wisconsin: I personally was a non-responder after two courses of hepatitis B vaccines administered in 1988 and 1990. We utilized an escalating-dose intradermal protocol recommended by the employee health group in 2000 at my previous institution. We checked my serologies after each dose, and I did respond after the second dose and have sustained my titer since that time.

Interestingly, I had itching and induration with each dose, and ended up with permanent hyperpigmentation at the sites, similar to what is sometimes seen with positive tuberculosis skin tests. This has always made me suspect that the improved conversion with the intradermal administration is secondary to improved stimulation of T-cell activity.

Louisiana: I have used Engerix-B 0.1 ml intradermally (ID) in physicians who need protection but have failed multiple courses of intramuscular (IM) vaccinations. Usually they develop a positive hepatitis B surface antibody following the second dose (given 30 days after the first dose). We first looked at the use of intradermal hepatitis B vaccination with the original vaccine, Heptavax-B. (Rev Infect Dis. 1990 Nov-Dec;12(6):1035-43.) This study was in vaccine-naïve patients and ID worked very well. As new vaccines became available, we used them and continued to have statistically similar results as with standard IM dosing with 1.0 ml (20 mcg). The ID route is not FDA approved but many vaccines are given ID and work well. In one patient I have had, I did need to go to 0.2 ml ID of Engerix-B to get him to develop measurable antibodies and develop a lasting Hep B surface antibody response.

Connecticut: High dose revaccination and intradermal vaccination have both been shown to work. Two references are below.

Ramsey KM, Ramsey GD, Herbert DE, Wilson PC, Givens PI, Green WK, Aikens TM. Successful Revaccination of Healthcare Workers with Prior Non-response to Hepatitis B Vaccines. Program and Abstracts of the 15th Annual Meeting of SHEA 2005: 44. p 71.

Levitz RE, Cooper BW, Regan HC. Immunization with high-dose intradermal recombinant hepatitis B vaccine in healthcare workers who failed to respond to intramuscular vaccination. Infect Control Hosp Epidemiol 1995 Feb;16(2):88-91.



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