Low-Dose Intradermal Flu Vaccine Effective as
Intramuscular
Daniel M. Keller, PhD
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.
