San Francisco Chronicle - Friday, May 18, 2007
*Margaret I. Johnston, Anthony S. Fauci

Most "classical" vaccines against viral diseases -- seasonal influenza, polio, and rabies -- stimulate antibodies (protective proteins) that control the virus, prevent disease and ultimately rid the virus from the body. However, inducing such effective antibodies against HIV is an extraordinary challenge because the virus has multiple ways of evading the body's immune defenses.

HIV rapidly mutates; and these variants of HIV change continually, and an infected person's immune system invariably cannot keep up with all of them. In addition, within days of infection, HIV begins to destroy critical immune cells that would normally protect against the virus; this attack on the body's defenses is relatively unique. Finally, HIV inserts itself into the DNA of human cells where it can remain undetected by the immune system. Even with extended drug therapy that reduces virus in the blood to undetectable levels, HIV is not eradicated from the body. These challenges have made it extremely difficult to design a vaccine that prevents an infection from establishing itself in the body.

In the face of these enormous scientific challenges, will a vaccine that can help control the AIDS pandemic ever become a reality? A "non-classical" approach to HIV vaccine development is evolving. Research in animal models of AIDS has demonstrated that vaccines that stimulate immune cells, called T cells, which do not attack the virus directly, but can recognize and kill HIV-infected cells, might be beneficial even if the vaccine does not completely prevent HIV infection. In animal models of HIV disease, vaccines that induce these types of T cells and that were given before the animals were exposed to virus blunted the magnitude of the initial infection, preserved immune-fighting cells, and resulted in a longer disease-free period.

Thus, a non-classical HIV vaccine given before an individual is exposed to the virus may not prevent initial infection or eliminate HIV or prevent disease entirely, but it might induce T cells that control HIV, contain the virus at low levels, and substantially delay the need to start drug therapy. In addition, because the efficiency of transmission of HIV from one person to another is directly related to the level of virus in the transmitting partner, restricting the virus to very low levels could lessen or even halt person-to-person HIV transmission. A vaccine that achieved these objectives could have a huge individual and public health benefit in mitigating the HIV epidemic.

In previous clinical trials, several experimental HIV vaccines have induced strong T-cell responses, yet many years of expanded clinical trials will be required to test the potential utility of these non-classical vaccines. Two such large, international trials have already started and a third may be initiated later this year, each requiring thousands of volunteers.

We must move cautiously along this uncharted path. If such a non-classical vaccine proves to be effective in clinical trials, the vaccine would need to be delivered as part of a multifaceted, comprehensive HIV prevention program so that recipients minimize or eliminate behaviors that expose them to HIV. Otherwise, any beneficial effect of the vaccine could be eliminated.

An effective HIV vaccine is our best hope of preventing the approximately 14,000 new HIV infections that occur daily worldwide. Research to design a classical vaccine that prevents HIV infection must continue. Given the urgent need to identify improved HIV prevention tools, however, we must pursue all promising avenues, including non-classical vaccines.

Today, HIV Vaccine Awareness Day, we also want to thank all the past, current and future community volunteers and researchers who are working to make a successful preventive HIV vaccine a reality. Their combined efforts and long-term commitment are critical if we are to be the generation that stops the relentless spread of AIDS (www.bethegeneration.org).

*Margaret I. Johnston, Ph.D., is director of the Vaccine Research Program in the Division of AIDS at the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health. Anthony S. Fauci, M.D., is director of the National Institute of Allergy and Infectious Diseases.
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