Quest For Effective HIV Vaccine Presents New Possibilities, Challenges

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HIV Vaccine

A vaccine that prevents HIV infection remains an important goal in the fight against AIDS, but the current top HIV vaccine candidates may not work in this way.

Rather, the first successful preventive HIV vaccines, if administered prior to HIV infection, may reduce HIV levels in the body, thereby delaying the progression to AIDS and the need to start antiretroviral drugs. These vaccines may also reduce the chance that a person infected with HIV would pass the virus on to other people, according to NIAID Director Anthony S. Fauci, M.D., and Margaret I. Johnston, Ph.D., director of NIAID's Vaccine Research Program in the Division of AIDS.

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In a review article in the May 17 issue of The New England Journal of Medicine, Drs. Johnston and Fauci examine the daunting challenges posed by HIV, the evolution of HIV vaccine research, the role T cells may play in HIV vaccine effectiveness, and how the first successful HIV vaccine may fit into a comprehensive HIV/AIDS prevention effort.

Vaccines typically work by mimicking the effects of natural exposure to a specific microbe. Because of initial exposure, the immune system develops the ability to recognize the specific microbe and can protect the human body against it if it reappears. HIV, however, has thwarted scientists' efforts thus far to develop a classic preventive vaccine for the virus because of its ability to integrate into target cells and evade clearance by the immune system. The interaction between HIV and the immune system is complex, and how different HIV-specific immune responses help to control infection is only partially understood.

"The development of an HIV vaccine is a complex research challenge because the virus is unusually well-equipped to elude immune defenses," says Dr. Fauci. "Much progress has been made; however, we must continue research efforts to improve our understanding of HIV and how it evades the immune system, to design new vaccine candidates and to assess the most promising ones in clinical trials."

Dr. Johnston adds, "An important research challenge is to determine if these so-called T-cell vaccines that primarily induce a cellular immune response can have a beneficial effect by reducing viral levels and preserving critical cells needed to control infection. There will be a tremendous public health challenge as well, in an HIV vaccine that does not completely prevent the virus from establishing itself in the body."

Once HIV enters the body, it infects crucial CD4+ T cells, replicates, spreads throughout the body and establishes HIV reservoirs in lymphatic tissues. Within weeks of exposure, virus levels peak and then decline to levels that may remain low for months or years. It is believed that CD8+ T cells

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