Dose sparing with intradermal injection of influenza vaccine

N Engl J Med. 2004 Nov 25;351(22):2295-301. doi: 10.1056/NEJMoa043540. Epub 2004 Nov 3.


Background: The loss of half the U.S. supply of influenza vaccine due to contamination has created a critical shortage. Dose-sparing strategies that use intradermal delivery of vaccines may be one approach to consider.

Methods: We conducted a randomized, open-label trial outside the influenza season in 100 healthy adults 18 to 40 years of age to compare the immunogenicity and safety of intradermal immunization with influenza vaccine with standard intramuscular immunization. Subjects were randomly assigned to receive either a single intramuscular dose of 0.5 ml of trivalent influenza vaccine, containing at least 15 microg of hemagglutinin per strain, by means of a prefilled syringe or a single intradermal dose of 0.1 ml, containing at least 3 microg of hemagglutinin per strain, by means of a fine-gauge needle; both injections were in the deltoid region. Changes in the hemagglutination-inhibition (HAI) antibody titer were assessed by comparing geometric mean titers and fold increases relative to baseline values and by comparing changes in the seroconversion and seroprotection rates. Local and systemic adverse events were assessed after both types of vaccination.

Results: Subjects who received an intradermal injection with one fifth the standard dose of influenza vaccine had increases in the geometric mean HAI titer by a factor of 15.2 for the H1N1 strain in the vaccine, 19.0 for the H3N2 strain, and 12.4 for the B strain on day 21, as compared with respective increases by a factor of 14.9, 7.1, and 15.3 for the intramuscular injection of the standard dose. Seroconversion and seroprotection rates were similar in the two groups on day 21, ranging from 66 to 82 percent and 84 to 100 percent, respectively. Local reactions were significantly more frequent among recipients of intradermal injections than among recipients of intramuscular injections, but such reactions were mild and transient.

Conclusions: In this study of young adults, intradermal administration of one fifth the standard intramuscular dose of an influenza vaccine elicited immunogenicity that was similar to or better than that elicited by intramuscular injection. Intradermal administration could be used to expand the supplies of influenza vaccine, but further studies are needed before this strategy can be recommended for routine use.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Viral / blood*
  • Female
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology
  • Humans
  • Influenza A virus / immunology*
  • Influenza B virus / immunology*
  • Influenza Vaccines / administration & dosage*
  • Influenza Vaccines / adverse effects
  • Influenza Vaccines / immunology*
  • Influenza, Human / immunology
  • Influenza, Human / prevention & control*
  • Injections, Intradermal
  • Injections, Intramuscular
  • Male


  • Antibodies, Viral
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Influenza Vaccines