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GETTING A VACCINATION FOR HEPATITIS
B, CHICKEN POX OR MUMPS MAY ONE DAY BE AS SIMPLE AS APPLYING A LOTION,
ACCORDING TO STANFORD RESEARCHERS. The scientists
believe that the needle-free delivery system they perfected in mice
can also provide relief to children lining up for annual vaccinations
and travelers seeking protection from exotic diseases.
Using a DNA solution containing a gene for the hepatitis
B virus, the researchers tried the simplest possible approach for
getting it into the body. They parted the mouse's fur and covered
a dime-sized area of skin with the liquid. When they tested the
mouse's blood one month later, they found that it contained antibodies
against the hepatitis B virus, confirming that the gene in the DNA
solution had entered skin cells and had started producing the foreign
protein, or antigen. After that, the mouse's immune system began
manufacturing antibodies against the unwelcome viral fragments,
just as it would if the antigen had been introduced the traditional
way, via an injection into the muscle.
"The simplest way worked -- just dropping it on,"
says Paul Khavari, MD, PhD, associate professor of dermatology.
He is senior author of the article in the September 1999 issue of
Nature Biotechnology that describes the team's findings.
Khavari and Hongran Fan, PhD, a clinical instructor in the lab and
lead author of the paper, were both surprised that, to their knowledge,
no one else had thought of such an obvious approach. "Even yourself,
you see the most simple thing and you wonder why you didn't think
of it sooner," says Fan.
In fact, researchers in Khavari's lab first tried
adding a vaccine directly to the skin in 1993. They were using the
technique as a control method in other experiments and were surprised
when it appeared to work. The team has been working on it slowly
since, but the pace of research and development will probably quicken
now that Stanford has licensed the technology to Redwood City-based
Maxygen Inc., for commercial development.
Meanwhile, Fan will continue her research. "There
are lots of differences between mice and humans and we don't know
if the immune system will respond in the same way," she says. One
key difference between the two that may have a dramatic impact on
the success of the painless delivery method is the amount of hair
on the skin.
The researchers found that the DNA solution is making
its way into the skin via hair follicles, and humans have fewer
hair follicles per square inch of skin than mice do. The team has
yet to determine how significant this difference will be, but their
experiments have shown that only a few hair follicles need to be
affected before the animal will mount an immune response against
the vaccine. In fact, less than one percent of the hair follicles
retain the DNA solution, according to Fan.
Khavari believes that these follicles may be in a
specific phase of their growth cycle that makes them amenable to
absorbing foreign materials. "The follicles are open for business,
in a sense, during the early anagen phase," he says. "The hole is
there but it is not sealed tightly around the hair." According to
Khavari, it may be this period that also renders the follicles susceptible
to invasion by bacteria, accounting for folliculitis -- a common
human infection.
Khavari and Fan believe that using skin, rather than
muscle, as the site of vaccination will prove to be effective for
many different diseases and may even elicit a stronger protective
immune response. "Muscle is not a primary site of antigen exposure,
whereas skin is bombarded continuously by microbes," says Khavari.
"The potency of an immune response to small amounts of antigen may
be much greater in skin."-- KRISTIN WEIDENBACH
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