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CDC HIV/AIDS/Viral Hepatitis/STD/TB Prevention News Update

A Basis of HIV Resistance Suggests New Vaccine Strategy




 

Lancet (05.19.01) Vol 357; No 9268: P 1594 - Wednesday, May 23, 2001

A few people remain HIV-negative despite continuous exposure to the virus. Findings from an ongoing study by a team of researchers headed by Dr. Rupert Kaul of the Weatherall Institute of Molecular Medicine, Oxford, United Kingdom, reveal that the cause may be that their immune response involves cytotoxic T lymphocytes (CTL) against the surface region of antigens -- called epitopes -- not recognized by most infected people. "The fact that infected and protected women focus their CTL response on different HIV epitopes could be a significant finding for vaccine development," Kaul said.

Kaul and colleagues studied the immune responses of sex workers in Nairobi, Kenya: women who have more than 60 unprotected sexual encounters with HIV-positive men annually. Women new to the group show high rates of seroconversion in the first year, yet some remain HIV-negative for three years and longer. Researchers compared the immune responses of 91 HIV- negative sex workers from the cohort with those of 87 HIV- positive sex workers. The two groups of women both mounted HIV-1 specific CTL responses -- but often against a completely different set of epitopes. A few women who remained HIV negative for several years before seroconverting showed a switch in response from one set of epitopes to the other, according to a study by the same team published in the Journal of Clinical Investigation (2001; 107: 341-49).

According to Kaul, "the only way to demonstrate a true causal relationship between CTL responses and HIV protection is to induce these CTL in the setting of a vaccine trial." Phase I testing of a vaccine developed by Andrew Michael of the Weatherall Institute is underway in Oxford and Nairobi. "The vaccine in this trial does include the seronegative-specific epitopes, as well as epitopes known to induce a strong CTL response in HIV-positive workers." Previous attempts to develop CTL-inducing vaccines have assumed that any CTL response could be protective, according to Jose Esparza, coordinator of the World Health Organization-UNAIDS HIV Vaccine Initiative. Future research should attempt to elicit protective CTL responses by taking into account the clade of HIV prevalent in the area to be targeted, and also should include epitopes tailored to the distribution of HLA types in the population, Kaul said. "The HLA types in Kenya have not been extensively studied but we are finding them to be quite different to those mapped elsewhere," said Kaul. Esparza agrees but cautions that "this would be particularly challenging in Africa, where both the genetic variability of the virus and of the host population is the largest." Esparza expects interim results in one to two years from the first HIV-vaccine phase III efficacy trial -- the rgp120 HIV vaccine -- being tested in the United States and Thailand. "We do not know how effective that vaccine will be, or whether it will be effective at all. It may be prudent to prepare for the worst and to consider the use of a low efficacy vaccine while research continues to develop more effective products," he said.



 


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Information in this article was accurate in May 23, 2001. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.