|
AIDS
vaccine clears first hurdle
Livestock virus is the
vector for agent that works in monkeys; nasal administration seen as plus.
A vaccine that uses an attenuated
livestock virus as a vector for two HIV proteins has kept infected monkeys
free of AIDS for more than a year, according to a team led by Yale scientists.
The vaccinated monkeys, some infected with a highly pathogenic simian
AIDS virus for as long as 14 months, have not developed full-blown AIDS
and their viral loads have remained low. The vaccine shows promise in
another area; it can be administered through nasal drops rather than by
injection, making it more affordable and practical for use in developing
countries, where AIDS is taking its heaviest toll.
“Based on our results
we think it is likely that this vaccine could be an effective AIDS vaccine
in humans,” said John K. Rose, Ph.D., professor of pathology and
of cell biology. Rose and his wife, Nina F. Rose, Ph.D., an associate
research scientist, led a team that included scientists at Yale, the Aaron
Diamond AIDS Research Center, Tulane University, Duke University and the
Gladstone Institute of Virology and Immunology. Their results were published
in the September 7 issue of Cell and presented at the AIDS Vaccine
2001 Conference in Philadelphia in September.
The virus, vesicular stomatitis
virus (VSV), is a preferred vector for vaccines because it provokes a
strong immune response. Although never tested in humans, VSV has proved
effective in animal models as a vector for influenza and measles vaccines.
The combination of the virus and two HIV proteins called Env and Gag put
the monkeys’ immune systems on high alert, making them more effective
against HIV, John Rose said.
“It is a very strong
stimulator in both arms of the immune system—the antibodies and the
cellular immune system,” he said. “This holds down the spread
of the infection in the animals. There are fewer infected cells. It is
less of a task for the immune system to hold the virus in check and the
viral loads go down to very low or below detection.”
The ability to deliver the
vaccine in drops rather than through needles, said Rose, is crucial in
developing countries. “It would be impractical and very expensive
to inject millions of people with DNA vaccines,” he said. “The
VSV-based vaccine would be a cost-effective and equally successful alternative
to other vaccines that have been tested.” In addition, the vaccine
proved far more effective when administered nasally than when injected
intramuscularly.
In two studies carried out
over the past four years, the team vaccinated seven monkeys and left eight
monkeys in a control group with no vaccination. All 15 monkeys were then
infected with a hybrid of human and simian AIDS viruses. “We found
that seven out of the eight unvaccinated monkeys developed AIDS in an
average of five months, while vaccinated monkeys have been AIDS free for
up to 14 months,” Rose said.
Wyeth Lederle Products Corp.
has licensed rights to the vector and is conducting further animal tests
in collaboration with Yale scientists before proceeding to clinical trials.
|
