May 18, 2015
Vaccination has historically been the best method for protecting against and ultimately defeating mankind's most devastating infectious diseases. Although the path to developing a safe and effective HIV vaccine has so far been difficult, achieving this goal remains key to realizing a durable end to the global HIV/AIDS pandemic.
HIV vaccine development has been challenging largely because of the unique characteristics of the virus. HIV mutates rapidly in the body, evading immune responses and thwarting vaccination attempts. And unlike infections with other viruses, only a minority of individuals infected with HIV develop broadly neutralizing antibodies, a powerful type of antibody that is capable of fighting an array of HIV strains and attacking key sites on the virus. In those individuals who do develop broadly neutralizing antibodies to HIV, these antibodies generally appear only after several years of infection.
Although many scientific approaches to an HIV vaccine have been attempted since the late 1980s, only one large trial-the RV144 study in Thailand-has demonstrated a modest degree of success. In the years that followed the RV144 trial, scientists, using samples from the study, have uncovered clues about antibodies that may have helped protect certain vaccine recipients.
To build on the success of RV144, a diverse set of public and private organizations, including the National Institute of Allergy and Infectious Diseases (NIAID), formed the Pox-Protein Public-Private Partnership, called P5, which aims to produce a safe and effective HIV vaccine and further scientific understanding of the immune responses associated with protection against HIV infection. Today, P5 researchers are working to both improve and prolong the protective effect seen in the RV144 study by using an extra vaccine boost and alternative adjuvants to increase antibody durability.
Earlier this year, NIAID and its P5 collaborators launched HVTN 100, a clinical trial in South Africa that is testing an investigational HIV vaccine regimen based upon the findings of the RV144 trial. The HVTN 100 vaccine regimen was designed to increase the magnitude and duration of vaccine-elicited immune responses observed in the Thai trial, targeting the HIV subtype that is most prevalent in South Africa. A vaccine that is safe and effective in preventing HIV infection in southern Africa could have a significant public health impact, as the burden of HIV/AIDS is greatest in that region of the world. The HVTN 100 clinical trial is the first of several planned trials and research studies connected to the P5.
Basic research on HIV is also characterizing the viral targets for HIV vaccines in fine detail. For example, in 2014, NIAID scientists and funded researchers identified the complete structure and conformation of the spikes on HIV that the virus uses to bind to the cells it infects, providing a clearer picture of how the virus fuses with a cell and the ways in which it evades detection by the human immune system. Now that researchers have an in-depth knowledge of the atomic structure of the HIV surface protein, scientists can better understand how it assembles and interacts with the broadly neutralizing antibodies that target the virus. This collective knowledge could eventually lead to an effective HIV vaccine that teaches the immune system to neutralize the virus.
A complementary approach to vaccine development is the direct administration of those antibodies that we hope the vaccine would elicit. NIAID researchers continue to evaluate the intravenous administration of VRC01, a broadly neutralizing antibody that is being tested in early-stage trials in both HIV-infected and uninfected adults. Results are expected soon, and if promising, NIAID may further evaluate the antibody in larger clinical trials as both a potential prevention modality and HIV treatment. Complementary approaches, such as vaccines that induce the body's T cells to kill HIV-infected cells, also are being pursued.
Researchers also have made progress in understanding how broadly neutralizing HIV antibodies develop. If a vaccine could stimulate the immune systems of those without HIV infection to produce these antibodies, the antibodies might protect against infection. Last year, a team of researchers led by the NIH discovered a new, potent HIV-neutralizing antibody, called 35O22, and the novel location on the virus to which it binds. Also, NIAID-supported scientists as well as collaborators at NIAID's Vaccine Research Center gained new insight into the induction of broadly neutralizing antibodies, which were found to cooperate with other, more ordinary antibodies to develop their broadly neutralizing capability. Scientists are using these insights and others to inform efforts to induce the antibodies with a vaccine.
The number of new HIV infections and AIDS-related deaths worldwide have decreased by more than one-third in the past decade largely because of extraordinary advances in HIV prevention and treatment. However, far too many people continue to become infected with HIV and die from AIDS-related causes. On HIV Vaccine Awareness Day, we recognize and thank the thousands of HIV vaccine clinical trial volunteers, researchers, health professionals, activists and others who continue to work to find a safe and effective preventive HIV vaccine. NIAID stands with you and renews its commitment to conducting and supporting the necessary research to develop a safe and effective HIV vaccine.
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