Low-Dose Intradermal Flu Vaccine Effective as Intramuscular

Daniel M. Keller, PhD

October 24, 2011

October 24, 2011 (Boston, Massachusetts) — Injecting a lower dose of 2010/11 trivalent influenza vaccine (TIV) intradermally was more immunogenic than a traditional full-dose intramuscular injection for chronically adults, Ivan Hung, MD, clinical assistant professor in the Department of Medicine at the University of Hong Kong, China, reported here at the Infectious Diseases Society of America (IDSA) 49th Annual Meeting.

Dr. Hung and colleagues used 1 of 2 devices to administer intradermal injections using 20% or 60% of the standard dose, and compared the immunogenicity with standard doses delivered intramuscularly in an open-label, prospective, randomized trial.

From December 2010 to March 2011, 282 chronically ill adults were randomly assigned to 1 of 4 treatments: TIV containing 3 μg of hemagglutinin antigen per strain, administered with a MicronJet600 device; the same treatment but with 9 μg of hemagglutinin antigen per strain; 9 μg of Intanza9 vaccine, administered with the Soluvia device (Sanofi-Aventis); and 15 μg of TIV administered intramuscularly (control group).

Immunogenicity was determined through a hemagglutination inhibition assay at baseline and 21 days after vaccination.

Of the 282 subjects enrolled, 262 completed the study — approximately evenly divided among the 4 groups (63 to 68 per group.) Demographically, the groups were similar, with a median age of 73.5 years (range, 68.0 to 78.5 years).

At day 21, the seroconversion rates for influenza A/H1N1 for all the intradermal lower-dose groups were higher (approximately 50%) than for the intramuscular full-dose group (approximately 13%; P = .017). Similarly, seroprotection, determined by hemagglutination inhibition assay, was greater for all the intradermal groups than for the intramuscular group (P = .024).

In all cases, seroconversion, seroprotection, and geometric mean titer fold increases were at least as good or better for the intradermal groups than for the intramuscular group in terms of response to the A/H1N1, H3N2, and influenza B components of the vaccines.

"The reason for that is perhaps [because] the intradermal vaccination attracted dendritic cells, and that actually mounted a much better immune response," Dr. Hung said, also noting that no serious adverse effects were detected.

He recommends that all elderly and immunocompromised individuals receive intradermal influenza immunizations to compensate for their reduced reactivity to vaccines.

"Intradermal vaccination actually mounted a much better immune response, and that would offer better protection against influenza and the complications of influenza (for example, pneumonia) in the elderly population and also for those immunocompromised hosts," Dr. Hung told Medscape Medical News. "For the lower dose, you have slightly fewer side effects in terms of swelling, in terms of redness, which is important for elderly people and perhaps has less systemic effects."

He explained that intradermal injection is quite easy to give, and suggested that intradermal dose reduction might be an effective way to make vaccine go further in situations of high demand during future pandemics, once the efficacy of dose-sparing vaccination in healthy individuals has been demonstrated.

Andrew Pavia, MD, chief of pediatric infectious disease at the University of Utah, Salt Lake City, and chair of the Pandemic Influenza Task Force of the IDSA, who was not involved in the study, told Medscape Medical News that it is worthwhile investigating better ways for influenza immunization.

"The weakness of flu vaccine is that it doesn't cause as good an antibody response in the elderly. One of the things that we'd like to do is to get a flu vaccine or a way of delivering the old flu vaccine that works just as well in the frail elderly as it does in healthy young and middle-aged adults."

Besides the equivalent or better efficacy that Dr. Hung showed, Dr. Pavia sees other advantages of intradermal injections. "There have been reports that with intradermal devices, it hurts much less going in because the needle is a microneedle, which people barely feel, but there may be increased itching or redness at the site, compared to getting a deeper injection with an intramuscular vaccine. Some people may prefer itching to injection pain," he said. "The efficacy studies really haven't been done to show that they're truly equivalent. Cost would be the only other barrier. I think as an alternative, this is very interesting and potentially very useful."

He also sees intradermal injection as an advantage for people who are "relatively needle-phobic." "It may be useful when you've got a less-skilled population because this is pretty much an automatic device — you don't have to be skilled in giving an intramuscular injection, and of course, there's less risk of needle sticks," he explained.

The study received no commercial funding. Dr. Hung reports a collaboration with and receiving research support from NanoPass Technologies. Dr. Pavia has disclosed no relevant financial relationships.

Infectious Diseases Society of America (IDSA) 49th Annual Meeting: Abstract 533. Presented October 21, 2011.


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