Intradermal vaccinations may stretch supply

Articles encourage some physicians, frustrate others

Two new studies suggest intradermal delivery of a reduced dose could expand the supply of influenza vaccine. This approach may be a promising way to address critical shortages of the flu vaccine, such as those experienced across the country this year. At least one physician, however, doesn’t agree.

The two studies appeared in the Nov. 25 issue of the New England Journal of Medicine. Since editors of the journal thought the articles had potential public health implications, they also released them early on the web site Nov. 3 (see

The first study, by Kenney et al, compared the immunogenicity and safety of intradermal flu vaccination to that of the standard intramuscular immunization in 100 healthy adults 18 to 40 years old.1

The randomized, open-label trial took place outside the flu season. The researchers found that intradermal administration of one-fifth the standard intramuscular dose "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," they conclude.

In the second study, by Belshe et al, researchers randomly assigned 119 adults to receive an intradermal injection of a reduced dose of the flu vaccine and 119 adults to receive an intramuscular injection of the standard dose.2 The two groups were subdivided by age: 18-60 years, and older than 60 years.

The researchers found that as compared with the intramuscular injection, the intradermal injection resulted in "similarly vigorous antibody responses among persons 18 to 60 years of age but not among those over the age of 60 years."

Experts dispute results’ implications

One infectious disease specialist found the results encouraging. "If other studies were to confirm those findings, it would certainly increase our vaccine supply substantially," says Keri K. Hall, MD, assistant professor in the department of internal medicine, division of infectious diseases, at the University of Virginia Health System in Charlottesville.

Another specialist was more critical, saying this approach has been discussed since the 1940s. "There are probably 15 to 20 publications that have said the same thing over the years," says Robert B. Couch, MD, professor of medicine and professor and chairman of microbiology and immunology at Baylor College of Medicine in Houston. "While it is an alternative in certain healthy primed populations to make the same amount of antibody you can get out of the standard shot — provided it is given correctly, which is a potential risk — there are no data anywhere to my knowledge that says it is equally protective. You don’t want to recommend something that has not been proven to be equally protective."

An editorial accompanying the articles in the journal argues that it is "our responsibility" to pursue the intradermal route and other approaches "to advance our ability to meet the inevitable challenges of emerging and reemerging infectious diseases, particularly influenza."

Through current studies as well as previous reports, it is becoming clear that use of the intradermal approach "may at least partially overcome the relatively poor influenza-specific immune responses seen in certain at-risk populations, particularly the elderly, in whom the immune response in general is known to diminish with age," say editorial authors John R. La Montagne, PhD, and Anthony S. Fauci, MD, former deputy director and director, respectively, of the National Institute of Allergy and Infectious Diseases, National Institutes of Health in Bethesda, MD.

"Moreover, in times of shortage, the dose-sparing intradermal approach might be particularly well suited to the young, healthy persons included in the CDC’s [Centers for Disease Control and Prevention’s] high-priority group for vaccination, such as health care workers, as well as to younger, otherwise healthy populations in general," they continue.

It is important to conduct further basic and clinical research to see if this approach could translate into a clinical benefit for healthy persons and for those in groups at high risk for flu-related illness and death, the authors say.

Even if the intradermal approach sounds promising, most physicians are waiting for the further research and for the go-ahead signal from the CDC. "I think that most hospitals and physicians would probably wait to see if the CDC will promote that approach," Hall says. "We won’t be pursuing that yet at our institution until we get some guidance from CDC about whether that is an appropriate approach to using the vaccine."


1. Kenney RT, Frech SA, Muenz LA, et al. Dose sparing with intradermal injection of influenza vaccine. N Engl J Med 2004; 351 (in press).

2. Belshe RB, Frances KN, Cannon J, et al. Serum antibody responses after intradermal vaccination against influenza. N Engl J Med 2004; 351 (in press).