Cautious Hope for an HIV Vaccine
Three years into the epidemic—in 1984—the secretary of U.S. Health and Human Services, Margaret Heckler, announced to the world that an HIV vaccine would be ready to test in two years. In 1997, President Clinton—mirroring President Kennedy’s challenge to get to the moon in ten years—called for a national goal to develop an effective HIV vaccine in the same length of time, saying, “it is no longer a question of whether we can develop an AIDS vaccine, it is simply a question of when. And it cannot come a day too soon. If America commits to find an AIDS vaccine and we enlist others in our cause, we will do it.”
But now more than 30 years into the epidemic, segments of the scientific community remain only cautiously optimistic when asked if a vaccine for HIV may ever be developed.
Scientists have every right to be cautious. Thus far, vaccine studies with human participants have failed or provided only modest protection. The most successful vaccine trial completed to date—the Thai RV144 study—demonstrated that people who received a “prime-boost” combination vaccine were 31% less likely to become infected with HIV.
Standing in the way of vaccine research is a missing model of natural immunity. Most viral infections for which there are vaccines—like smallpox or the measles—were developed using clues about how the body naturally clears the infection. A “fundamental tenet of vaccinology,” say Margaret Johnston and Anthony Fauci in the New England Journal of Medicine, is that “the best way to develop an effective vaccine is to design a candidate that mimics infection and induces responses akin to natural immunity.”
It’s difficult to apply this strategy to HIV because there are no individuals who have been able to clear HIV naturally—the body’s immune response is either too slow to prevent HIV from establishing reservoirs in the body or wholly ineffective at clearing HIV once infection is established. Once HIV begins to replicate (i.e., make new copies of itself), it mutates and changes—ensuring its survival by evading the reach of HIV medications, treatments or immune responses that may target only one specific part of the HIV machinery or replication process.
“There’s no question that one of the biggest challenges is that a vaccine against HIV is not only going to have to deal with the incredible global diversity of the sequence of this pathogen—but we also have to think forward. About how the virus is going to evolve in any individual that is infected after the vaccine is given. So we have to think about vaccines that can deal with the enormous diversity in the virus,” said Galit Alter, of the Ragon Institute of MGH, MIT, and Harvard during a keynote speech delivered at CROI 2015.
Another challenge is the speed with which HIV establishes reservoirs in the body—setting up shop in places where it can “hide” from the immune system. Scientists now estimate that an effective vaccine will have to induce an immune response within the first two days after exposure to the virus.
HIV vaccine research diverges along a few different paths. One line of promising research focuses on broadly neutralizing antibodies (bNAbs)—antibodies that prevent many different strains of HIV from infecting host cells and engage the immune system by “tagging” cells that do get infected for destruction. Another line of vaccine research uses direct DNA injection or vectors (non-HIV viruses that don’t cause disease) to deliver HIV genes into the body, causing the immune system to mount an anti-HIV response. Trials testing new prime-boost combinations—the strategy used in the RV144 trials—are expected to begin in South Africa in 2016. There are more than 20 different vaccine trials now in various stages of development and testing, which you can get an overview of here.
To learn more about HIV vaccines, watch the following videos produced by Youreka Science in collaboration with Bridge HIV of the San Francisco Department of Public Health.
In Vaccines 101, learn what a vaccine is, how it “trains” the immune system before viral exposure, the characteristics of HIV that make vaccine development challenging, about the most successful HIV vaccine clinical trial conducted to date, and why participating in a vaccine clinical trial will never cause an HIV infection.
In Clinical Trials 101, learn about what it takes to test a potential vaccine and the clinical trial process that all vaccines go through before they can be approved by the Food and Drug Administration.
You can find more information about the development of these educational videos, here.
Additional HIV vaccine awareness day materials from AVAC can be found here.