Watch NIAID Director Anthony S. Fauci, M.D., discuss current HIV vaccine research approaches.Developing a safe and sufficiently effective HIV vaccine is essential if we are to achieve a timely and durable end to the global HIV/AIDS pandemic. The path to an HIV vaccine has not been—and will not be—an easy one. In the 27 years since the first HIV vaccine clinical trial was performed, we have been disappointed by many promising investigational vaccines that ultimately proved ineffective in clinical trials, encouraged by a large-scale study in Thailand that demonstrated for the first time that an HIV vaccine can provide a modest level of protection, and, heartened by recent important discoveries about antibodies that may be capable of protecting against a wide range of HIV strains.

HIV is uniquely challenging as a vaccine target because, unlike other viruses, it elicits antibodies capable of killing a wide range of HIV strains (called broadly neutralizing antibodies) in only a minority of those who become infected and only after several years of infection. Furthermore, HIV is also extremely genetically diverse and mutates rapidly to evade immune responses. But through important basic research discoveries, scientists have made substantial progress in understanding how broadly neutralizing HIV antibodies develop and the specific sites on the virus to which they bind, which will lead to promising new targets for future HIV vaccine candidates.

For example, NIAID scientists and grantees, using blood samples from a newly HIV-infected person, were able to chart the co-evolution of the virus and the antibodies created in response to infection. In the past year, researchers have highlighted the regions of HIV where these antibodies bind to block infection and revealed the structure of the HIV protein that is responsible for allowing HIV to enter human immune cells and cause infection. They also found the mechanism responsible for stabilizing key HIV proteins and hiding sites where some of the most powerful HIV neutralizing antibodies attach themselves and conducted a vaccine study in nonhuman primates using a simian version of HIV (SIV) that yielded insights into controlling and clearing infection. Additionally, scientists have also made advances in understanding T-cell responses that may be important to vaccine-induced immunity against HIV. By applying insights gained from each of these discoveries, researchers may be able to develop a vaccine that mimics the natural development of antibodies but creates them rapidly enough to prevent HIV infection.

NIAID researchers are currently evaluating the intravenous administration of a broadly neutralizing antibody called VRC 01 in early-stage trials in both HIV-infected and uninfected adults. If the two studies indicate that the approach is safe and can block the virus, NIAID may evaluate the antibody in clinical trials involving a larger number of adults and infants born to HIV-infected mothers who did not receive prenatal care or antiretroviral therapy to prevent mother-to-child HIV transmission.

Scientists also continue to explore findings from the RV 144 HIV vaccine study in Thailand, which, in 2009, provided the first evidence that an HIV vaccine can provide a modest level of protection. For example, looking at serum samples collected from participants in the Thai trial