Positive results in an HIV vaccine trial conducted in more than 16,000 Thai volunteers, announced this morning, need to be examined more closely to analyze data on subgroup analyses and specific immune responses so that subsequent trials can absorb that information, says the principal investigator of the only other ongoing efficacy trial of an HIV vaccine.

"It's basically a shot in the arm for the HIV vaccine field," Columbia University clinical virologist Scott Hammer told The Scientist. "Any positive news out of HIV vaccine work is important." Hammer, who is the PI on the HIV Vaccine Trials Network 505 (HVTN 505) trial, said that he's encouraged by the preliminary results coming out of Thailand -- in that trial the vaccine appears to have decreased HIV infection risk by about 31% -- and that the positive results point to the crucial role of human testing in the development of any vaccine. "I think what this really tells us is that clinical trials that look for activity of efficacy of vaccines are an absolutely necessary component of vaccine discovery." Hammer added that human immune system variability or virus diversity can't really be mimicked by any of the currently used laboratory animal models.

The HVTN 505 trial, which started recruiting participants about a month ago and has enrolled about 30 people thus far, is what Hammer called an "advanced Phase II" trial that will seek to investigate the effects of an HIV vaccine on modulating the viral load in any of the 1350 participants who end up contracting the virus. Like the Thai trial, the HVTN 505 trial uses the "prime-boost" regimen -- where a first round of injections readies the immune system to recognize and combat HIV and a second ramps up immune activity -- but uses a different vector and different vaccine contents.

The vaccine regimen tested in Thailand consisted of priming shots of a canarypox vector carrying three synthetic HIV genes and booster shots of a recombinant form of gp120, a surface protein found in HIV clades B and E. The HVTN 505 study, which is being co-sponsored by the National Institute of Allergy and Infectious Diseases, will administer three priming shots of a recombinant DNA-based vaccine with three HIV genes from clade B followed by booster shots containing the adenovirus serotype 5 (Ad5) vector with HIV viral envelope genes from clades A, B and C.

Tom Hassell, vice president for vaccine development at the International AIDS Vaccine Initiative, told The Scientist that though there are differences between the vaccines used in the Thai and HVTN 505 trials, Hammer and his colleagues will certainly learn from the Thai results. "There's going to be an intense effort in trying to spot the correlates of protection from the Thai study," Hassell said. "It's not the same materials that are being used, but the principles will be the same. If we're able to understand what's driving the efficacy, we'll be able to have an early view with the 505 study of what might be successful."

Hammer agreed. "We'll be looking very hard at these data and deciding the importance of them on the 505 trial," he said.

Though the Thai trial is providing promising initial data, 30% efficacy is on the low end of the spectrum regarding the vaccine's potential licensure, explained Hassell. Vaccines typically achieve efficacies of 60-90% before they are officially licensed by the US Food and Drug Administration, he said. This means that the results will spur further research, but the world will have to wait longer for a safe and effective HIV vaccine.

Ironically, the 505 vaccine, which was developed by the NIH's Vaccine Research Center, also faces an uphill licensure battle, even if its positive results outpace those coming out of the Thai trial. This is because of the taint associated with the Ad5 vector after the much-publicized failure of Merck's STEP trial (see The Scientist's coverage here), in which an Ad5-based vaccine may have increased HIV infection risk in some study participants. For this reason, Hammer said, the current HVTN 505 trial very carefully narrowed the eligibility requirements for volunteers, and the researchers are viewing the study as more proof of concept than testing a licensable vaccine candidate.

The full results of the Thai trial are set to be released at an international AIDS vaccine conference in Paris near the end of October.


Related stories:

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[20th July 2009]

New wrinkle for HIV vaccine
[25th February 2009]

HIV vaccine research: crisis of faith?
[24th April 2008]