Researchers Taking Side Roads to HIV Vaccine

BETHESDA, Md., May 18 -- The road to an HIV vaccine has been unexpectedly bumpy, largely because of some unusual characteristics of the virus, two leading researchers say.

The obvious approach -- developing a vaccine that uses viral antigens to generate a completely protective antibody response -- has so far failed, according to Margaret I. Johnston, Ph.D., and Anthony S. Fauci, M.D., both of the National Institute of Allergy and Infectious Diseases here.

That's because of HIV's enormous genetic diversity and because of some unique features of the viral envelope protein, Drs. Johnston and Fauci said in the May 17 issue of the New England Journal of Medicine.

For that reason, researchers are turning their attention to vaccines that will elicit killer CD8+ T-cell responses, in the hope, not of protecting against infection, but of blunting the initial viremia and prolonging disease-free survival.

"There is optimism that a T-cell vaccine could be beneficial in helping to control HIV infection," they said, even if it doesn't completely prevent it.

Indeed, Drs. Johnston and Fauci said, more than a dozen such vaccine candidates are in various stages of clinical trials around the world.

In animal models, there is evidence that a T-cell vaccine lowers the initial burst of viremia and preserves the memory CD+ cells. A key question, the authors said, is whether a vaccine that had those properties would benefit the vaccinated individual.

Studies have shown that a lower viral "set point," a function of the level of the initial viremia, appears to correlate with slower disease progression.

If that proves to be true in practice, "people who receive T-cell vaccines before infection might remain disease-free for a prolonged period," Drs. Johnston and Fauci said, "and antiretroviral therapy, which can be burdensome and have serious side effects over time, might be delayed."

There is also evidence that such a vaccine might slowly erode the reservoir of HIV-infected CD4 cells, and lower the risk of sexual transmission of the virus, they added.

On the downside, they acknowledged, a partly effective T-cell vaccine would pose public health challenges.

"The medical community would need to deliver it as part of a broader HIV-prevention program to reduce, if not eliminate, high-risk practices," Drs. Johnston and Fauci wrote. "Otherwise, the individual and public benefit could be counteracted by an increase in exposure to HIV."

The classic protective vaccine "remains the goal," they concluded, but it might not be realized with the first generation of HIV vaccines. But even a partly effective vaccine, they said, "could benefit both individual recipients and the at-risk community."