On his wall at the University of Washington, Larry Corey, principal investigator of the HIV Vaccine Clinical Trials Network (HVTN), has a plaque that reads, “If at first you succeed, try hard not to look astonished.”
There weren’t many researchers who met that challenge after hearing the initial results of RV144 on September 24. The canarypox vector-based ALVAC in combination with a genetically engineered version of gp120 known as AIDSVAX showed a modest 31.2% efficacy in preventing HIV acquisition—the first evidence of efficacy in any AIDS vaccine clinical trial. In the hours and days following the announcement, we interviewed scores of researchers and many of them shared the same sentiment: surprise. Even some of the study’s investigators were caught off guard when they were whisked away to an army base in California to be briefed on the results during what they thought was a trip to attend the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.
The results from RV144 were unexpected in part because of how these candidates had performed in previous trials. RV144 also got off to a rocky start. Just after its launch, the trial was publicly scrutinized by a cadre of leading AIDS vaccine researchers, who published a policy forum in Science magazine questioning the scientific rationale for the trial.
But now another sentiment seems to prevail among many AIDS vaccine researchers: optimism. This best describes the mood at the AIDS Vaccine 2009 conference, which took place from October 19-22 in Paris. At the conference, detailed analyses of the data from RV144 were shared and discussed, and the emphasis shifted from the controversies of the past to the way forward. This trial provides a clue, actually 8,000 of them, that may help solve the mysteries of immunological protection against HIV. This is the first chance researchers have had to try to dissect the correlates of protection in humans—a finding that would undoubtedly lead to the development of improved candidates and a renewed sense of hope that vaccine-induced protection against HIV is not an insurmountable task.
Additional research findings showcased in Paris provided more promising news. Significant advances with other vectors, newly discovered neutralizing antibodies against HIV, and lessons from trials of failed candidates were also shared and contributed to the overall sense of optimism. Although much work remains to be done, it may be that in Paris the AIDS vaccine field picked up a much needed dose of joie de vivre.
—Kristen Jill Kresge, Managing Editor