Thai HIV vaccine trial follow-up studies offer possible explanation for HIV prevention success

Peter Gilbert and SCHARP researchers, HVTN Laboratory Program, part of worldwide effort to understand trial outcome, influence future HIV vaccine studies
Dr. Peter Gilbert led the Hutchinson Center's Statistical Center for HIV/AIDS Research and Prevention (SCHARP) group that, along with the HVTN Laboratory Program, provided the statistical design and analyses for the study. Image courtesy of Dr. Peter Gilbert

Hutchinson Center researchers played a key role in the discovery of important immune responses that may have protected some volunteers from HIV in the RV144 Thai trial, the first HIV vaccine trial to show modest effectiveness in preventing HIV infection. Results from extensive RV144 laboratory studies were published April 5 in the New England Journal of Medicine.

The RV144 study, conducted by the U.S. Military HIV Research Program and Thai Ministry of Health, showed in 2009 that a vaccine combination prevented about 31 percent of new infections in more than 16,000 adult volunteers. These data provided the first evidence in humans that a safe and effective preventive HIV vaccine is possible, and provided an opportunity to understand why this vaccine combination succeeded and how to improve upon it.

Identification of immune responses that reliably predict vaccine efficacy is a primary goal of vaccine research. Walter Reed Army Institute of Research and Duke University researchers collaborated with more than 25 institutions to analyze immune responses elicited in vaccine recipients. Dr. Peter Gilbert led the Hutchinson Center's Statistical Center for HIV/AIDS Research and Prevention (SCHARP) group that, along with the HVTN Laboratory Program in the Vaccine and Infectious Disease Division, provided the statistical design and analyses for the study.
"This unprecedented collaboration brought together investigators from all over the world to compare immune function tests to understand the outcome of the RV144 trial," said Duke University's Dr. Barton Haynes, who led the studies. "By studying those who became infected compared to those who did not, we believe we have found very important clues for how the RV144 vaccine regimen might have worked."
The researchers discovered that different types of antibody responses were associated with a higher or lower rate of HIV infection. IgG antibodies, specific to a particular region called V1V2 of the HIV outer coat (envelope protein) correlated with lower infection rates among those who were vaccinated. The hypothesis is that when IgG antibodies bind to the V1V2 region, they might help prevent infection.

The researchers also found that vaccine recipients with the highest blood levels of a different type of envelope-binding antibody, IgA, appeared to have less protection from HIV than those with low levels. Scientists hypothesize that these IgA antibodies to a different region of HIV envelope may have interfered with possible vaccine-induced protective responses.

"These findings represent a milestone in HIV vaccine development and have the potential to significantly enhance future HIV vaccine trials," said VIDD's Dr. Jim Kublin, HVTN's executive director.

Col. Nelson Michael, MHRP director and study coauthor, said these studies inform new testable hypotheses that, if validated, may help scientists prioritize vaccine candidates for future clinical trials, potentially accelerating the development of a more efficacious vaccine.

"Different HIV vaccines may protect against HIV in different ways. More research is needed to fully understand these results, and to determine if they can be generalized to other types of HIV vaccines or similar vaccines tested against other regional types of HIV or via different routes of exposure," he said.

"These studies reinforce and extend the results seen in the RV144 trial and provide new insights that may lead to a better and longer-lasting HIV vaccine," said senior author Col. Jerome Kim of the MHRP.

[Adapted from a U.S. Military HIV Research Program news release]

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