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Intradermal Immunization: An Approach to Maximizing the Flu Vaccine Supply

Intradermal injection of flu vaccine may elicit nearly the same immune response as intramuscular injection, but with much lower doses.

Flu vaccine shortages and ongoing concerns about avian flu highlight the need to optimize flu vaccine use. One potential approach is to vary the immunization route. Intradermal immunization, for example, delivers antigen directly into the skin, which contains large numbers of antigen-presenting dendritic cells. Two research groups recently investigated this approach.

Kenney and colleagues enrolled 100 healthy adults aged 18 to 40 in a government- and industry-sponsored, randomized, open-label trial comparing a single 0.5-mL intramuscular dose of the 2003-2004 inactivated flu vaccine (i.e., 15 µg of hemagglutinin each from an H1N1 influenza A virus, an H3N2 influenza A virus, and an influenza B virus) with a single 0.1-mL intradermal dose of the same vaccine (3 µg of each hemagglutinin). On day 21, the two groups showed similar rates of seroconversion and seroprotection (defined as a strain-specific hemagglutination-inhibition antibody response 1:40) against all three influenza strains included in the vaccine. Significantly more intradermal than intramuscular vaccinees experienced local reactions to the vaccine, including erythema (96% vs. 8%), pruritus (42% vs. 4%), swelling (84% vs. 10%), and induration (34% vs. 8%). No serious related adverse events occurred in either group.

In a similar industry-sponsored, open-label trial, Belshe and colleagues randomized 238 adults 18 years old to receive a single 0.5-mL intramuscular dose of the 2003-2004 inactivated flu vaccine or a single 0.1-mL intradermal dose of an experimental vaccine containing 6 µg of hemagglutinin each from an H1N1 influenza A virus, an H3N2 influenza A virus, and an influenza B virus. In the 130 subjects aged 60, immune responses against all three influenza strains were comparable in the two vaccine groups. Among the 108 participants aged >60, a somewhat stronger immune response was seen in those who received the intramuscular vaccine; the difference was significant only for antigen to the H3N2 strain. Nevertheless, 100% of the intradermal vaccinees aged >60 achieved seroprotective antibody levels against the H1N1 and B strains, and 93% had seroprotective levels against the H3N2 strain. In both age groups, signs of local inflammation were significantly more common in intradermal than in intramuscular vaccinees; among intradermal vaccinees, injection-site pain occurred significantly less frequently in younger than in older participants. No serious vaccine-related adverse events were reported.

Comment: In these studies, intradermal injection of inactivated flu vaccine elicited nearly the same immune response as did intramuscular injection, but with a significantly lower dose of vaccine. Using lower doses could ease the current flu vaccine shortage in the U.S. and could also stretch supplies, should a flu pandemic occur. Still, these are pilot studies; large-scale investigations are needed to confirm the efficacy and safety of this vaccination dose and route.

— Richard T. Ellison III, MD

Published in Journal Watch Infectious Diseases November 22, 2004

Citation(s):

Kenney RT et al. Dose sparing with intradermal injection of influenza vaccine. N Engl J Med 2004 Nov 25; 351:2295-301; http://content.nejm.org/cgi/doi/10.1056/NEJMoa043540.

• Original article (Subscription may be required)
• Medline abstract (Free)

Belshe RB et al. Serum antibody responses after intradermal vaccination against influenza. N Engl J Med 2004 Nov 25; 351:2286-94; http://content.nejm.org/cgi/doi/10.1056/NEJMoa043555.

• Original article (Subscription may be required)
• Medline abstract (Free)