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The quest for an effective HIV vaccine presents new possibilities, challenges

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--so-called killer T-cells--are responsible for this reduction in HIV levels; however, their ability to continue to suppress the virus declines over time as the virus mutates and the immune system is progressively destroyed.

The infection of CD4+ T cells occurs very early in HIV disease, and virus persists indefinitely. Other viruses also replicate robustly but, unlike HIV, most do not establish a permanent reservoir of infected cells in the body. The window of opportunity to prevent long-term HIV infection may close permanently once a pool of latently infected cells is in place, Drs. Johnston and Fauci note. Neutralizing antibodies, which can attach to and eliminate free virus, only appear after HIV levels have declined substantially. Further, the effectiveness of these antibodies is stymied because of the rapid genetic changes that occur in HIV’s outer envelope protein, which allow the virus to escape detection.

While early efforts to develop an HIV vaccine focused on the viral envelope, an improved understanding of how HIV causes disease has brought inc
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Source:NIH/National Institute of Allergy and Infectious Diseases


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