Vaccine and Infectious Disease Division

Identifying the unique qualities of HIV-resistant individuals

A small number of individuals, called “exposed seronegatives”, remain uninfected despite being repeatedly exposed to HIV-1.  Over time, some exposed seronegatives eventually become HIV-1 infected.  By studying the immune responses of these individuals, scientists may discover insights into how to better design HIV-1 vaccines and treatment therapies.  To better understand how these individuals are able to withstand infection, VIDI member Dr. Julie McElrath, VIDI affiliate member Dr. Tuofu Zhu, and colleagues studied the virus, genes, and immune response of one exposed seronegative man who became HIV-1 infected after more than 2 years of unprotected sexual exposure to at least one HIV-1 infected partner and other partners with unknown HIV status.

By analyzing blood samples from this person before and after HIV-1 infection, the scientists found that he produced a wide array of HIV-specific immune responses even before HIV-1 infection, or seroconversion, but at lower levels of intensity than those detected after seroconversion.  In addition, half of the responses detected before infection were directed to a different region of the virus than the responses that were measured after the infection. The scientists also found that although this individual has a gene known to protect against HIV-infection, B27, the gene was not activated until after infection occurred.  

Therefore, the pre-infection immune responses present in the individual studied were ultimately not able to prevent HIV infection.  Similar detailed studies of other exposed seronegative individuals may help identify the immune responses that are critical in protecting against HIV-1 infection– knowledge that may prove important in designing a successful HIV-1 vaccine.

Preinfection human immunodeficiency virus (HIV)-specific cytotoxic T lymphocytes failed to prevent HIV type 1 infection from strains genetically unrelated to viruses in long-term exposed partners.  Liu Y, Woodward A, Zhu H, Andrus T, McNevin J, Lee J, Mullins JI, Corey L, McElrath MJ, Zhu T.  J Virol. 2009 Oct;83(20):10821-9.

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