AIDS 2008: A Changing Landscape for Vaccine Research

Understanding the Immune System and AIDS Vaccine Strategies 

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By Regina McEnery

AIDS vaccine researchers were unexpectedly pushed in new directions 11 months ago, following the suspension of immunizations in the STEP trial involving 3,000 volunteers. The vaccine candidate known as MRKAd5, made by genetically altering a common cold virus to include fragments of HIV, showed no efficacy in preventing HIV infection or in reducing the amount of virus in the blood of individuals who subsequently became HIV infected through natural exposure to the virus. Later, researchers observed a trend toward increased susceptibility to HIV infection among certain sub-groups of trial volunteers—uncircumcised men who have sex with men (MSM) who had pre-existing immunity to the modified cold virus that was used as a vector because of being naturally exposed to the same type of cold virus before.

Following MRKAd5’s disappointing performance, at least one large vaccine trial was curtailed and others were put in limbo. Researchers, meanwhile, are returning to the laboratory to re-evaluate current approaches to AIDS vaccine development, with a focus on basic discovery research. Major funders of AIDS vaccine research, such as the US National Institute of Allergy and Infectious Diseases (NIAID), are trying to attract new investigators and spark novel ideas about how to induce broadly neutralizing antibodies against HIV and determine the precise role of mucosal immunity in HIV prevention.

This shift in priorities is now expected to dominate much of the discussions at the sprawling XVII International AIDS Conference in Mexico City, August 3-8. This biannual AIDS conference is expected to attract about 25,000 participants and is generally seen as a venue for activists, advocates, and policymakers, rather than an arena for breakthrough AIDS research.

“My experience attending these meetings is you just never know the issues that will attract the most attention,” says Anthony Fauci, director of NIAID. “But superimposed over all the discussions in Mexico City will be a topic that will be huge: Where do we go in the direction of AIDS vaccine research?”

NIAID announced on July 17 that it would not conduct the proposed version of the PAVE 100 trial that would have involved testing a combination of two vaccine candidates developed at the Vaccine Research Center at NIAID, one of which is similar to MRKAd5. The PAVE 100 trial was designed to enroll 2,400 volunteers. Fauci made the final decision regarding the trial after consulting with the scientific community and AIDS vaccine advocates during a meeting of the AIDS Vaccine Research Subcommittee on May 30 at which opinions about the trial were solicited (seeVAX June 2008 Spotlight article, Nearing a Decision on PAVE). Plans to test the VRC candidates have not altogether been scrapped. NIAID will consider funding a smaller, more focused trial that is designed to look solely at whether the combination of candidates can lower the quantity of virus circulating in individuals who become HIV infected through natural exposure despite receiving the vaccine candidates, according to a statement released by NIAID. This much-anticipated decision came just two weeks before the start of the Mexico City conference and will likely draw attention there. Fauci is gearing up to answer questions about the decision during a special satellite session he will participate in (“Looking to the Future: The Epidemic in 2031 and New Directions in AIDS”).

Pedro Goicochea, an AIDS researcher with Investigaciones Médicas en Salud in Lima, Peru, who is participating in another symposium on the future direction of vaccines and microbicides, says this AIDS conference will be an opportunity to clarify lingering questions about the STEP trial results and vaccine efficacy trials in general. “The explanations were so technical,” says Goichochea. “It is still a work in progress trying to find out what happened and the community doesn’t have the message clear.”

Goichochea said that three pre-exposure prophylaxis (PrEP) trials, which are testing oral antiviral drugs as preventive measures against HIV, will likely be a major topic at the conference as well.

Myron Cohen, an immunologist with the Center for HIV/AIDS Vaccine Immunology who is delivering one of the conference’s plenary talks, said the devastation caused by the 27-year-old epidemic makes the long-term goal clear. “We have to continue to extend every [available] strategy for prevention,” he says. “We have no choice but to [also] try and make a vaccine. We have to keep trying to identify how we modify immune responses in such a way to prevent HIV.” Cohen says the AIDS vaccine community also has to let go of the notion that scientists will find the equivalent of a home run.

Pedro Cahn, president of the International AIDS Society, the organization that sponsors the conference, says universal access to treatment and prevention will also be major themes at this conference. “Some voices are being raised regarding too much money being spent on AIDS and that this could be seen as detrimental for other healthcare services,” says Cahn. “We think it’s exactly the opposite. Really, the provision of AIDS services has helped strengthen healthcare services.”