What are Vaccines for HIV Prevention and Therapy?
Today there are no HIV vaccines which can prevent HIV infection. All of the candidates being studied are in the experimental stage. Preventive vaccine candidates are being tested in HIV-negative people. Some of these candidates are being tested to see if they can prevent infection. Other candidates are being tested to see if they lower viral load in people who receive the vaccine before becoming HIV infected but can learn to partially fight the resulting infection.
In 2012, investments in global preventive HIV vaccine R&D were virtually flat—increasing by just US$2 million over the previous year to total US$847 million. While funding has gradually declined since 2007, the field has responded with attempts to increase efficiency by forming collaborations to better utilize the collective knowledge and research infrastructure of organizations and institutions globally.
Four years ago, the vaccine regimen used in the RV144 trial in Thailand showed 31.2 percent efficacy against HIV infection by the end of the study, providing the first evidence that a safe and effective preventive HIV vaccine is possible. Analysis of the study in 2012 and early-2013 provided additional insight into the vaccine’s effectiveness. Collaborating researchers from the MHRP, the National Institute of Allergy and Infectious Diseases (NIAID) of the NIH, Duke University and the Thai Ministry of Public Health, along with 25 other institutions, discovered immune response clues that may have played a role in protecting some trial volunteers from HIV, finding that different types of antibody responses were associated with a higher or lower rate of HIV infection. Further research confirmed these results and provided insights into variables that may have influenced the efficacy seen in RV144. These findings have sparked new research, including a trial to see if the results can be repeated and improved in a high-incidence setting, an adaptive design trial looking at multiple vaccine candidates and an efficacy trial using the same regimen as in RV144 in an MSM population in Thailand.
With more than 30 candidates moving forward in clinical trials, basic research to identify biological mechanisms that can be translated into new vaccine candidates has increasingly become a focus in the HIV vaccine field. Research funded by several of the largest investors—including the US NIH, the International AIDS Vaccine Initiative (IAVI) through USAID, the Bill & Melinda Gates Foundation (BMGF) and private pharmaceutical and biotechnology companies—is enabling the discovery and further study of broadly neutralizing antibodies that block the HIV virus’ ability to infect cells. Analysis of the structure and evolution of antibodies and the way that they bind to HIV is being used to design new antigens to elicit antibodies through vaccination. Human clinical trials to test these concepts are in planning stages.
In 2012, the BMGF and US NIH invested a significant portion of their resources in antibody-related research. Other major funders of antibody- related research include the European Commission (EC), and the government of the Netherlands. Investments in antibody-related research were especially crucial for collaborations seeking to utilize expertise across different organizations, such as NIAID’s Centers for HIV/AIDS Vaccine Immunology & Immunogen Discovery (see Box 5), the IAVI-coordinated Neutralizing Antibody Consortium (NAC) and the European Consortium on Neutralizing Antibodies Using gp41 (EuroNeut-41).
Excitement about advances along the entire HIV vaccine research continuum in 2012 and prior years was tempered by the early futility finding in April of 2013 from the HVTN 505 vaccine trial. Immunizations under HVTN 505, the only large ongoing efficacy trial of a candidate vaccine, were halted by its Data Safety and Monitoring Board due to milestone findings that the vaccine used in the trial was not effective. The trial, funded by the US NIH, was estimated to cost between US$75 million and US$80 million.