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HIV Vaccines: Progress and Prospects

Just a few days after many of the leading researchers in the AIDS vaccine field gathered for the HIV Vaccine Summit (see Spotlight, this issue), they reconvened in vastly different environs for the annual joint Keystone Symposia on HIV Vaccines and HIV Pathogenesis. This year’s meeting took place from March 26 to April 1 in Banff, Canada, and like the field itself, was more focused on fundamental immunology and discovery research. 
Many speakers remarked in some way on the results of the STEP trial and its repercussions. Larry Corey of the University of Washington said during his opening keynote presentation that the STEP trial has “recalibrated” the HIV vaccine field, but he dismissed the notion that nothing positive has come out of it and made it clear that in his estimation, the results from the STEP trial do not mark the end for vaccine candidates that stimulate T-cell responses and not neutralizing antibodies (see Primer, this issue). “The ability to make such vaccines may be more approachable than getting effective neutralizing antibody vaccines,” Corey said.

Researchers presented some updated data from the ongoing analyses of the trial. Susan Buchbinder of the San Francisco Department of Public Health, and a principle investigator on the STEP trial, said there was a two- to three-and-a-half-fold increase in risk of HIV infection in the vaccine group as the level of antibodies against adenovirus serotype-5 (Ad5), which was the modified cold virus used as the vaccine vector, increased. Corey and Buchbinder addressed possible explanations for this observation. The majority of volunteers in the trial were men who have sex with men and so one possible mechanism is that more Ad5-specific CD4+ T cells were present in the rectal mucosal tissues, creating more targets for HIV, according to Corey. He also said an indirect biological mechanism could be at play and that perhaps the vaccine candidate interfered with the body’s innate or natural immune responses against HIV. Buchbinder said analyses of other potential confounding factors—including sexual networks, clusters of infections, and changes in sexual behavior—which may also help explain this observation are still ongoing (see VAXFebruary 2008 Primer on Understanding Biostatistics and the STEP Trial).

Efforts to more fully understand mucosal immunology (see VAX January 2008 Primer on Understanding HIV Transmission), the types of T-cell responses a vaccine should induce (see Primer, this issue), and the mysteries of individuals who are HIV infected but are able to control the virus (long-term nonprogressors), all figured prominently at this meeting and remain clear priorities for the field. “There isn’t one way forward or one simple way forward,” said Alan Bernstein, executive director of the Global HIV Vaccine Enterprise. “If anyone says there is they’ve got a crystal ball that I don’t have.” —By Kristen Jill Kresge