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Microbiologist
Richard Compans is developing a secret weapon—a genetically
engineered virus replica that can be used as a vaccine against avian
flu.
“We have produced a non-infectious
recombinant particle that contains both the core proteins and the
exterior surface proteins of the avian influenza virus, but it lacks
the viral genetic material,” explains Compans, chair of the
Emory School of Medicine’s Department of Microbiology and
Immunology. “We think that such a vaccine could be produced
faster and under much safer conditions than traditional flu vaccines
and that it could be more closely tailored to emerging new strains
of flu.” |
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While
other experimental avian flu vaccines have successfully produced
an immune response in people, it was often too low to prevent infection.
Building on his previous work on a VLP against HIV, Compans also
plans to incorporate adjuvants—additional molecules—into
the vaccine to enhance its ability to induce protective immunity.
"We are calling this a chimeric VLP vaccine, because we’re
inserting new molecules to enhance the potency of the vaccine,"
Compans says. He believes he can develop a VLP vaccine that will
activate immune responses, including both neutralizing antibodies
as well as long-term antibodies and cell-mediated immunity.
VLPs copy the structure of authentic
viruses but are not infectious, making them safer to produce than
vaccines using live, but weakened, organisms. They are recognized
by the immune system as the "real" virus upon immunization,
causing the body to produce antibodies, but not causing illness.
When a person is exposed to the real thing, the immune system releases
antibodies to protect against infection. The influenza VLPs contain
multiple copies of the major influenza surface protein, the hemagglutinin
(HA) protein, which binds to cell surfaces. Antibodies to the HA
protein are responsible for blocking infection by the virus.
Emory and Georgia Tech collaborators
have already developed an influenza VLP that has been tested in
mice exposed to a mouse-adapted strain of flu. The next step is
to develop a VLP that specifically resembles H5N1 (the current avian
flu strain) and test it in poultry exposed to the live virus. The
VLP should be ready to test in about a year. |
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Hitting
a moving target
Even
before avian flu emerged as a possible pandemic threat, concerns
were mounting about the cumbersome process required to produce the
traditional flu vaccine. Each year, public health officials gather
data on the strains that are circulating in people to determine
which three strains are likely to cause the most serious illness
during the peak flu season. Once these strains are chosen, the viruses
are injected into fertilized hen’s eggs. The viruses must
then grow inside chicken embryos before the eggs can be broken open
and
the virus harvested. It then must be purified and chemically treated
to produce enough killed-virus vaccine to inoculate most of the
population.
Because up to six months may lapse
between the time the strains are chosen and when a vaccine is available,
sometimes a strain not included in the vaccine turns out to be the
season’s most prevalent virus. When this happens, the vaccine
is less effective.
And with avian flu, scientists learned
early on that traditional vaccine production technology wouldn’t
work at all. "It’s a highly pathogenic avian virus, so
when it’s injected into the eggs it rapidly kills the embryo
and then the virus can’t grow," Compans says. The VLP
technology will address this problem. Because VLPs can be produced
in cell cultures, without the long process of growing live virus
in chicken eggs, newly identi-fied circula-ting strains can be rapidly
incorporated into the vaccine. And because the VLPs are not infectious
themselves, there is much lower risk to vaccine production workers,
and more sites should be able to produce the vaccine.
"Right now, there is potential
risk because you have people working with live virus to inoculate
the eggs," Compans says. "Only a few sites have facilities
that can provide an appropriate protected environment. This results
in limited production capacity as well as greater risk to workers." |
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Feeling
no pain
Emory and Georgia Tech are working not just
on a new vaccine but also a new way to administer it. Compans’s
lab has partnered with Tech’s Center for Drug Design, Development,
and Delivery to work on a transdermal flu vaccine patch. Tech researchers
have developed microscopic needles that can be coated with a drug
or vaccine and then placed on the skin to inject the medication
painlessly. The microneedles—100 to 1000 micrometers thinner
than the width of a human hair—allow the drug to be injected,
which is more effective than cutaneous absorption. But the needles
are too small to stimulate nerve endings and result in pain, says
Mark Prausnitz, director of Tech’s center.
The center became interested in working
on microneedle applications in vaccines because of the skin’s
unique immune capabilities, says Prausnitz. "We have found
that there is something about the immune response in the skin that
permits us to use lower dosages than we would if the vaccine were
delivered the usual way."
The technology is well suited to vaccine
administration. Vaccine patches could be stored and transported
much more easily than current vaccine supplies. They likely would
not require refrigeration and could be stored for longer times under
less expensive conditions. And a patch would give the public health
system many more options to protect people, especially in the event
of a pandemic, Compans says.
"First, a painless vaccine will
be much more acceptable and we might see improved rates of vaccination,"
he says. "And whereas the current vaccine must be administered
by trained health care providers, a patch could be self-administered—people
could apply it to themselves. Some day, you might be able to get
your annual flu vaccine in an envelope in the mail." |
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