HIV vaccines: When is a failure actually a success?

The Thai trial, also known as RV 144, was published in the New England Journal of Medicine in 2009, and was the first HIV vaccine trial to show a protective effect, though this was just modest. In fact, in 30 years of HIV research, it has often felt like a vaccine was just around the corner, but that corner always seems to be just out of reach. However, a new study, also published in NEJM, has tried to unpack just how that protective effect worked, and has come up with some interesting observations that could help researchers target new vaccines more effectively.

In the RV144 trial, the people who were vaccinated with ALVAC HIV and AIDSVAX B/E had roughly a third lower chance of becoming infected with HIV compared with those in the control group who were not vaccinated. The researchers have found that of the 16,000 people vaccinated in the trial, those who produced high levels of an IgG antibody to part of the virus coat known as V1V2 were less likely to be infected. Those who had higher levels of an IgA antibody to another part of the outer coat, called C1, were less likely to be protected--this could suggest that these antibodies actually reduced the value of the vaccination.

"This analysis has produced some intriguing hints about what types of human immune responses a preventive HIV vaccine may need to induce," said Dr. Anthony S. Fauci, the director of the National Institute of Allergy and Infectious Diseases (NIAID), which collaborated with Walter Reed Army Institute of Research and Duke University. Col. Nelson Michael, U.S. Military HIV Research Program (MHRP) director and co-author of the study, noted: "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."

The researchers are looking to find the link between the V1V2 antibodies and the protection against HIV--do the antibodies cause the protection, or are they markers of the infection? And does the C1 antibody interfere with the vaccination? The answers could point a new direction for HIV vaccine research.

- read the press releases here and here
- see the abstract from NEJM (2012)
- check out the paper from NEJM (2009)

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