Trials of NIH HIV Vaccine Candidate Scaled Down After Failure of Merck Vaccine
Trials of NIH's Vaccine Research Center's HIV vaccine candidate will be scaled down after the recent failure of a Merck HIV vaccine candidate, Bloomberg reports (Lauerman, Bloomberg, 3/24). Merck in September 2007 announced it had halted a large-scale clinical trial of its experimental HIV vaccine after the drug failed to prevent HIV infection in participants or prove effective in delaying the progression of the virus to AIDS. The vaccine candidate also might have put some trial participants at an increased risk of HIV (Kaiser Daily HIV/AIDS Report, 3/21).
The VRC candidate, called PAVE-100, is similar to the Merck vaccine in that both stimulate CD4+ T cells against HIV and both contain the cold virus adenovirus-5. Researchers in the Merck trial found that men who received that vaccine were at an increased risk of contracting HIV if they had a high immunity to adenovirus-5 when they enrolled in the trial. Anthony Fauci, director of NIH's National Institute of Allergy and Infectious Diseases, said that the VRC trial will not enroll anyone with high immunity to the cold virus. According to Bloomberg, this could rule out nine in every 10 potential study participants in Africa. In addition, the trial will require that men be circumcised, according to Wayne Koff, senior vice president for research and development at the International AIDS Vaccine Initiative.
VRC initially planned to enroll 8,500 people in the U.S. and Africa in the trial but now plans to enroll only 2,000. In addition, IAVI on Monday announced plans to pull out of the VRC trial. Koff said the group had planned to enroll 1,000 people in Africa in the new trial but pulled out because it believes that human trials of HIV vaccine candidates should be small and aim to design better vaccine candidates than those currently in development. Koff said that there is not a "clear understanding of why" the Merck trial failed, adding that IAVI believes there is "a safety unknown" in the new VRC trial.
The new vaccine has features that could make it more effective than the Merck vaccine, according to Mitchell Warren, executive director of the AIDS Vaccine Advocacy Coalition. PAVE-100 uses DNA that researchers hope will induce cells to produce vaccine-like proteins to generate a protective immune response against HIV. Researchers also are hoping that the cold virus in PAVE-100 will cause a stronger immune response than the cold virus in the Merck vaccine. According to Warren, HIV vaccine trials in the immediate future should focus on answering questions about how such vaccines work as opposed to whether they can prevent HIV transmission. He added that there is "certainly something to learn by advancing PAVE-100."
According to Bloomberg, some researchers have said that the failure of the Merck vaccine has set back HIV vaccine research for years, and many researchers are questioning new trials. The AIDS Healthcare Foundation recently called for all HIV vaccine research to be stopped. NIAID on Tuesday is expected to hold a meeting with HIV/AIDS researchers to discuss its $497 million HIV vaccine research program. Bruce Walker, a researcher at Harvard Medical School, said the NIAID meeting will aim "to stop and take stock" of HIV vaccine development following the "unanticipated result" of the Merck trials (Bloomberg, 3/24).