The production of both cytotoxic T lymphocytes B often called "killer T cells" B and HIV suppressive factors may have played a role in protecting highly exposed female sex workers in Thailand from HIV infection, according to new data presented today by the Centers for Disease Control and Prevention (CDC)and the Thai Ministry of Public Health (MOPH).
The findings, presented at the 12th World AIDS Conference, follow three years of collaborative research between the two agencies. The research was designed to determine how a group of female sex workers in Thailand have remained uninfected after numerous exposures to HIV. Researchers believe these findings could have important implications for the future development of an HIV vaccine.
Increased understanding of the protective immune response found in these high-risk individuals may lead us closer to an effective vaccine," said Helene Gayle, M.D., M.P.H., Director of the CDC's National Center for HIV, STD, and TB Prevention. Gayle cautions that progress in prevention research is always incremental, and the full implications of these findings may not be known for several years, "Each new piece of the puzzle brings us one step closer to solving it, but none of the pieces can be viewed alone."
Researchers of the HIV/AIDS Collaboration, a joint activity of CDC and the Thai MOPH, first identified in 1994 a number of female sex workers in Chiang Rai, northern Thailand, who were highly HIV exposed but remained persistently seronegative (HEPS). A team led by Timothy Mastro, M.D., and Khanchit Limpakarnjanarat, M.D., identified these HEPS women among a group of brothel sex workers with an extremely high prevalence of HIV (47% infected) and a high rate of new infection (20% infected during the first year of follow-up).
When a virus enters the body, the body has two immune responses -- an antibody and a cellular response. The body produces antibodies specific to the invading virus, as well as cytotoxic T-cells specific to the part of the virus the immune system recognizes. The cytotoxic T-cells then try to kill off virus-infected cells to limit the extent of new virus production. Other immune cells have the ability to produce soluble factors that can prevent HIV from growing.
Researchers are working to determine which regions of HIV may produce an immune response, and if there are any differences between the type of immune response produced (i.e., the particular T-cells produced) seen in the HEPS versus the infected women.
CDC researcher Janet McNicholl, M.D., presented results which identify many new regions of the virus capable of inducing an immune response. Many of these regions are found in both subtype B (the subtype of HIV most common in the U.S.) and subtype E (the subtype of HIV most common in Southeast Asia)viruses.
In the same session, Busarawan Sriwanthana, Ph.D., from the Thai Ministry of Public Health, presented an analysis describing the regions of the virus that produced an immune response in the HEPS women. This study concluded that although the HEPS women and infected women produced T-cells specific to many of same regions of the virus, the response of HEPS women was weaker and to fewer regions. Researchers believe this may indicate that both the type of "killer T-cell" and the level play some role in the protective effect seen in the HEPS women.
Taken together, these findings suggest that to be effective, vaccines may need to induce very specific T-cell responses and that certain regions of the virus may be more likely to elicit a protective effect," said CDC's McNicholl. "They also tell us it will be important to ensure that the regions of the virus introduced as a component of a vaccine are consistent across subtypes."
In addition to conducting further analyses of the role of cellular T-cell production, CDC researchers are also working to analyze the possible contribution of soluble factors to the resistance of infection among the HEPS women. Soluble factors are substances secreted by the cells that are capable of suppressing the replication of HIV. In a related poster presentation, CDC's Salvatore Butera, Ph.D., finds that HEPS women in this study have a higher level of production of soluble factors. Butera concludes that soluble factor production, combined with T-cell production and other immune responses, may enable these women to clear the virus from their system.