Vaccine Improves Survival in Monkey Tests

by John S. James

Summary: A vaccine tested at the U.S. NIAID clearly improved the survival of monkeys, a benefit not predicted by T-cell and viral load tests. It was predicted by measurements of memory T cells in the first few months of infection -- giving important insights into how HIV disease develops, and how to test HIV vaccines early so that only the best candidates will go into large human trials.

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Researchers at the U.S. National Institute of Allergy and Infectious Diseases (NIAID) reported that an experimental vaccine clearly improved the survival of monkeys after infection by SIV (simian immunodeficiency virus), a virus similar to HIV -- even though it did not prevent infection, and did not much improve viral load or total T-cell count.

While the viral load and T-cell count did not predict the greater survival, something else did -- measurement of memory cells (one kind of T-cells) in the first few months of infection. Memory cells make up more than half of T-cells in adults, and early in HIV disease many of these cells are infected and eventually lost. In the monkey test, three to five times fewer of the memory cells were infected in vaccinated animals than in unvaccinated animals.

The vaccine used in this study was a simplified version of an HIV vaccine now in phase II human trials in the U.S. and some other countries.

Besides the possibility of a survival benefit in humans even if a vaccine fails to prevent infection, this is important for additional reasons:

• The researchers found an immune response from a vaccine that did help protect the animals. A big problem in HIV vaccine research has been that while it is easy to show immune responses to HIV vaccines, it has been very hard to find "correlates of protection" -- that is, responses that do any good at protecting against HIV-type viruses.
• If this result is confirmed in humans, it could give a much earlier indication of which vaccines are promising and which are not. This early information could help with another big problem in vaccine research. Since no one would deliberately infect people with HIV in order to test a vaccine, trials have to study thousands of people for years to prove that a vaccine works. Very few such studies can be done, so it is very important to get the best candidate vaccines into these large phase III trials. An early indicator that can be measured in every patient, and is known to predict survival, would help immensely.
• The fact that the monkeys benefited even partly creates a framework for studying HIV pathogenesis (development of the disease) -- and studying how vaccines might work, as well as immune-based or other new kinds of treatment for those already infected. Without the observed benefit to the animals, lots of data could still be collected, but it might be very difficult or impossible to know which findings were meaningful and which were not.

For More Information

NIAID published a press release, "Monkeys Vaccinated Against SIV Survive Longer After Infection" on June 9. You can find it at
http://www3.niaid.nih.gov/news/newsreleases/2006/SIVvax.htm

This press release includes references to the two articles, one in Science, and the other in Journal of Experimental Medicine.

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