(Submitted to F.I.C by Jody Lanard)

San Francisco Chronicle, Thursday, November 4, 2004

In the midst of a vaccine shortage that has left the nation with half its
supply of flu shots, researchers have found that injecting as little as
one-fifth the normal dose into the skin may be just as effective for most
Americans as the full dose delivered with the traditional jab in the arm.

A pair of studies released in advance of their publication later this month
in the New England Journal of Medicine provide strong evidence that the
country´s undependable flu vaccine supply can be stretched for healthy young
adults with a simple switch to intradermal injections -- commonly given in
allergy medicine.


"What it means is, we can get away with less,´´ said Dr. Anthony Fauci,
director of the National Institute for Allergy and Infectious Diseases and
co- author of an editorial accompanying the studies.


Slipped between layers of skin by a sleeker needle, the lower dose produced
the same robust immune response in adults under 60 years of age as the full
dose traditionally injected into muscle tissue. But the antibody levels
tapered off with age, and the experimenters found the lower dose was not as
effective for a group over 60.


The discovery has implications not only for the current run on flu shots --
caused when British regulators shut down the factory responsible for 48
million doses destined for the United States -- but also for stretching
vaccine supplies in a pandemic like the Spanish flu of 1918, when at least
20 million people died.


Federal authorities are unlikely to recommend the new technique this year on
the basis of just two studies. But doctors hoping to extend their supplies
of precious flu vaccine may decide to use it on younger patients who still
qualify for a flu shot -- such as pregnant women, health care workers and
those in close contact with infants under 6 months of age.


"The flu vaccine is not approved for intradermal use, but some physicians
will read the New England Journal of Medicine articles and, on their own
accord, will administer it ´off-label,´ " Fauci said in a telephone
interview.


Although the technique did not work as well in older patients, Fauci said
further studies might determine whether a full dose delivered into the skin
provided even better results than the same shot given in the traditional
manner.


Flu shots are up to 90 percent effective in preventing influenza among
healthy adults, but among the elderly the protective effect may dwindle to
as low as 30 percent. Immunization nevertheless can reduce deaths by 80
percent among elderly patients who still contract influenza.


In one study conducted by Dr. Robert Belshe and colleagues at Saint Louis
University School of Medicine, 119 subjects were given the equivalent of 40
percent of a normal flu dose, while a comparable group was given the
standard shot. When their immune responses were compared, there was no
significant difference between the two groups among those aged 18 to 60. The
over-60 group also had a strong response, but results were slightly better
among those who had the intramuscular shot.


Those who had the shot between the layers of skin reported more local
inflammation at the injection site. "We hypothesize that this is a good
thing, ´´ Belshe said.


Reduced doses of flu shots delivered into the skin concentrate the vaccine
in an environment rich in varieties of blood cells that serve as the body´s
first line of defense against microbial invaders.


Delivering a flu shot directly into this environment is a bit like
disturbing a hornets´ nest. It stirs up the immune system where it lives,
creating an inflammatory response that cranks up the number of antibody-
producing cells that ward off or weaken the virus.


The technique requires careful positioning of the needle and takes a few
more seconds to deliver than a traditional flu shot. That could pose
problems for mass immunization clinics, where the extra seconds can add up.


A second study by Dr. Gregory Glenn and colleagues at Iomai, a Gaithersburg,
Md., biotech company developing skin patches for vaccine delivery, found flu
vaccine worked just as well at one-fifth the normal dosage using the
transdermal technique in a group of healthy 18- to 40-year-olds.


Against the most potent strain of flu circulating, the technique actually
produced a stronger antibody response in the Iomai study.


The latest research results were no surprise to Dr. Hugh Merhoff, a retired
Red Bluff general practitioner. During the Asian flu pandemic of 1957, he
recalls, doctors at the Contra Costa County Hospital adopted the technique
after an allergist suggested it.


"It worked, and whenever we had shortages after that, I´d use it," he said.
"I´ve used it on myself.´´


Once he heard of the flu shot shortage, the 76-year-old Merhoff said he had
e-mailed local health officials and the Department of Health and Human
Services urging them to consider intradermal shots as a solution to the
crisis. "If you have half the vaccine, all you have to do is give half as
much to twice as many people,´´ he said.


For NIAID director Fauci, Tuesday´s encouraging news was vastly overshadowed
by the sudden death Tuesday evening of his colleague and co- author of the
New England Journal of Medicine editorial, NIAID deputy director John La
Montagne. La Montagne, 61, collapsed in a airport line after arriving in his
native Mexico City.


"Everybody agrees he was one of the finest, gentlest human beings anyone
ever met,´´ Fauci said. "He was one of the best infectious disease
biologists around. This is one of the worst days of my life.´´