Intradermal shots could stretch flu vaccine supply

Nov 4, 2004 (CIDRAP News) – Two studies just published by the New England Journal of Medicine (NEJM) suggest that injecting influenza vaccine just beneath the skin surface, instead of into muscle, may be a way to stretch flu vaccine supplies without sacrificing protection.

In one study, young adults who received one fifth of the standard vaccine dose in an intradermal shot showed at least as strong an immune response as others who received full-dose intramuscular shots.

In the second study, intradermal vaccination with 40% of a standard dose worked just as well as a standard intramuscular dose in adults aged 18 to 60. However, older adults showed a somewhat less vigorous response to the reduced intradermal dose.

"In times of shortage such as the present, intradermal vaccination of healthy young persons with reduced-dose inactivated influenza vaccine could be considered in order to stretch vaccine supplies," write Robert Belshe, MD, and colleagues, authors of the second study. NEJM published both studies online as early-release articles.

Intradermal vaccination involves inserting a needle 1 to 2 mm into the skin, according to the two reports. The method has been used with some success for hepatitis B and rabies vaccinations, but it is not approved for flu vaccination in the United States.

The study using young adults was conducted by a Gaithersburg, Md., company called Iomai, which is developing vaccine skin patches. Richard T. Kenney, MD, and colleagues recruited 100 healthy adults ranging from 18 to 40 years old and randomly assigned them to receive either a standard intramuscular dose of trivalent flu vaccine (15 micrograms [mcg] of hemagglutinin per strain) or a single intradermal dose at about 20% strength (3 mcg of hemagglutinin per strain).

As measured by increases in hemagglutination-inhibition titers 21 days after vaccination, the immune response in the intradermal group was similar to or better than that in the intramuscular group, the report says. Those who received intradermal shots had more local reactions to the vaccine, but the reactions were mild and transient.

The authors write that using reduced-dose intradmeral shots "is particularly appealing, because standard tuberculin syringes and needles can be used with multidose vials of influenza [vaccine] to increase the supply of influenza vaccine by a factor about five." But they add that further studies are needed to show the "wide-ranging relevance" of the technique.

In the other study, researchers from Saint Louis University, the University of Rochester, and GlaxoSmithKline assigned two groups of 119 people each to receive trivalent flu vaccine by intradermal or intramuscular injection. The intradermal shots contained 6 mcg of hemagglutinin for each strain, while the intramuscular shot contained the standard dose of 15 mcg for each strain. Each group was divided into younger and older subgroups—18 to 60 years and older than 60.

In the younger people, the two injection methods both yielded serum antibody responses that were "vigorous" and not significantly different. The older subgroups also had a strong antibody response to both types of vaccination, but the response was somewhat better in those who received intramuscular shots. However, the difference was significant only for one of the three viral strains in the vaccine (H3N2).

As in the other study, local reactions to the injections were more common among the intradermal group than the intramuscular group, but they were mostly mild.

The authors suggest that the intradermal injections could be used for younger members of two of the groups assigned priority for flu vaccine in the current shortage: healthcare workers and close contacts of infants younger than 6 months. The researchers add that the intradermal technique is harder to learn than the standard technique, but vaccinators would be likely to use the method effectively after training.

The two reports are hailed as significant in an accompanying editorial by the late John R. La Montagne, PhD, and Anthony S. Fauci, MD, of the National Institute of Allergy and Infectious Diseases (NIAID). "Both of the current studies clearly show that intradermal vaccination may have greater immunogenicity than intramuscular vaccination," they write. (La Montagne, who was deputy director of the NIAID, died suddenly this week.)

On the basis of the two new studies and previous reports on intradermal immunization, "It is becoming clear that use of the intradermal route may at least partially overcome the relatively poor influenza-specific immune responses seen in certain at-risk populations, particularly the elderly," La Montagne and Fauci write. They call for clinical trials in "a broad range of populations" to pave the way for approval of intradermal vaccination for flu.

Kenney RT, Frech SA, Muenza LR, et al. Dose sparing with intradermal injection of influenza vaccine. N Engl J Med 2004;351(22) (published online Nov 3) [Full text]

Belshe RB, Newman FK, Cannon J, et al. Serum antibody responses after intradermal vaccination against influenza. N Engl J Med 2004;351(22) (published online Nov 3) [Full text]

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