On July 13, the Obama administration unveiled a new national strategy to curb the AIDS epidemic, a plan whose stated goals include reducing the annual number of new HIV infections by 25% within five years. Motivating this crusade are a slew of sobering statistics, including an estimate from the Centers for Disease Control and Prevention that a total of 1,106,400 adults and adolescents were living with HIV infection in the U.S. at the end of 2006.
As Seth Berkley and Alan Bernstein—who are president and CEO of the International AIDS Vaccine Initiative (IAVI) and executive director of the Global HIV Vaccine Enterprise, respectively—wrote in The New York Times in July, “Ending HIV/AIDS urgently requires a vaccine. The evidence that a safe and effective HIV vaccine can be developed is stronger than ever.” This article provides a review of recent developments significant to the ongoing search for a viable vaccine candidate.
One notable advance was publicized in September 2009 by the U.S. Military HIV Research Program, which is focused on developing an effective HIV vaccine for use in Southeast Asia. In a six-year-long, community-based, Phase III trial known as RV144, researchers demonstrated that a combination of two vaccines—based on HIV strains that commonly circulate in Thailand—was safe and modestly effective in preventing HIV infection.
Specifically, the treatment consisted of a prime-boost combination of ALVAC® HIV and AIDSVAX® B/E vaccines. More than 16,000 adult volunteers in Thailand were involved in the study. Executed by the Thai Ministry of Public Health, the study included a team of leading Thai and U.S. researchers. The trial was funded by the U.S. government, specifically the Division of AIDS with the NIAID and the U.S. Army Medical Research and Materiel Command.
According to the trial sponsor, the U.S. Army Surgeon General via the U.S. Army Medical Materiel Development Activity, the results showed that the combined vaccines lowered the rate of HIV infection by 31.2%—a statistically significant amount—in a heterosexual population compared with placebo.
For the first time ever, the ability to reduce the risk of HIV infection in humans was demonstrated. This news was presented by the lead clinical investigator in October 2009 at “AIDS Vaccine 2009” in Paris and subsequently published in the New England Journal of Medicine.
In 2010, more than 30 U.S. and international collaborators initiated lab studies of the patient specimens in an effort to define the immune responses mediating the vaccine-induced protection against HIV infection. These efforts are ongoing, and further work is required to develop and test a vaccine suitable for licensure and worldwide use.
In separate news from July 2010, researchers from the NIAID Vaccine Research Center (VRC) reported in two Science papers on their discovery of three human antibodies that neutralize HIV. Two of these antibodies were shown to target a broad range of HIV strains. Nearly everyone infected with HIV produces some antibodies to it; the newly identified antibodies are unique in their breadth of neutralizing activity.
The VRC scientists screened blood samples from HIV-infected people around the globe for antibodies against nearly 200 strains of HIV to determine how many strains the antibodies of each patient could neutralize. Blood from one particular patient, known as “donor 45,” was found to include broadly neutralizing antibodies specific for HIV envelope proteins.
The screen identified three antibody-producing cells with the desired activity. Two of the cells, named VRC01 and VRC02, were found to neutralize 91% of the HIV strains tested, while a third, named VRC03, was found to neutralize 57%.
This finding lends support to the principle that it is possible for the human immune system to generate broadly neutralizing antibodies. However, as noted by the authors of these Science papers, the design of a vaccine that can induce antibodies with similar specificity will require significantly more effort.