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To stop the spread of the HIV epidemic and contribute to the development of a vaccine.

Frank Plummer has been the Canada Research Chair in Resistance and Susceptability to Infections at the University of Manitoba since January 1, 2001. Based on his experience examining individuals that exhibit a natural resistance to HIV, Plummer currently investigates the possibility of a genetic cause for HIV immunity and hopes the results of his work will foster the development of a vaccine against AIDS in the near future. Presently directs the National Microbiology Laboratory in Winnipeg.

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Dr. Plummer and colleagues will expand on past research that has identified groups of commercial sex workers in Kenya who do not become infected with HIV despite repeated sex without condoms. While the phenomenon is well documented, it is not well understood. The project will undertake a comprehensive analysis of these women’s immune systems and genetics. Understanding what makes them apparently immune to the virus could guide HIV vaccine and drug development.

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Research Plan

Videos

• Gates Grand Challenge Clip 1
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• Full Video (25 min)

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Bill and Melinda Gates Foundation

With more than 42 million people living with AIDS in the world today and an estimated 27 million people dead of AIDS, the development of HIV-1 vaccines is an ever more urgent goal. Most vaccines for infectious diseases of humans have been developed from an understanding, however imperfect, of what constitutes natural immunity. There is mounting evidence that some individuals are protected against HIV-1 infection.

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Most evidence suggests that these women are naturally immune to HIV. Although they don’t have antibody to HIV in their blood, their white blood cells are able to recognize and kill HIV infected cells. They also have HIV-1 antibody in their genital tract that is able to neutralize a broad range of HIV viruses.

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Scientists from the University of Manitoba Biology of Sexually Transmitted Infection CIHR Research Group have been studying the basis for resistance to infection with the AIDS virus (HIV) for the past 10 years. Working with a group of prostitutes who practice their sex trade in a slum in Nairobi, Kenya, they have identified a group of 120 women who remain HIV uninfected despite many years of exposure Evidence suggests that these women are naturally immune to HIV. Although they don’t have antibody to HIV, their white blood cells (WBC) are able to recognize and kill HIV infected cells. The WBCs, or killer T cells, of these women seem to be able to kill a broad range of HIV viruses. Understanding how these WBCs do this and why these women develop them could be the key to effective vaccines for HIV. Recently, the research group has discovered that there is clustering of HIV resistance in families. This suggests that there may be a gene or genes that permits the immune system of these women to develop protective immune responses. In a continuing study, the research team will study the families of these women to confirm that there is a genetic basis for HIV resistance and determine how it is inherited. They will determine if HIV resistance is linked to resistance to other infections and begin a search for the genes involved. This work could be very important in developing a vaccine for HIV, but could also lead to an understanding of resistance to other infectious diseases and how the immune system responds to infection.

Vaccination strategies that induce strong mucosal as well as systemic responses show promise in macaque models of HIV pathogenesis. Indeed, HIV specific effector immune responses at the mucosal surface are detectable in a high proportion of individuals who are resistant to HIV despite repeated exposure. HIV specific IFN-? secreting CD8+ T cells have been detected in approximately half of HIV resistant women from a highly exposed population of sex workers in Nairobi, Kenya.

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The majority of heterosexual transmission of HIV-1 occurs at the site of the genital tract. This is the first site of exposure to HIV in the majority of instances and immune responses at mucosal surfaces are likely to be critical in mediating protection against infection. HIV specific IgA capable of neutralizing a broad range of HIV isolates, and capable of inhibiting HIV transcytosis across epithelial surfaces has been detected in 70% of HIV resistance sex workers.

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MRSI has been collaborating with institutions based at Oxford University, the University of Ghent and Université de Montréal. The Kenya program has given birth to collaborations in India, where Manitoba scientists are applying their hard-won expertise in projects financed by the Canadian International Development Agency and the Bill and Melissa Gates Foundation.

For more information check out the collaborators page and the publications page