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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.