Since efforts to develop a preventive HIV vaccine began in the 1980s, tension has existed between advocates for quickly moving vaccine candidates into human testing (an "empirical approach") and those seeking more basic research on HIV and immune responses to natural infection as a critical precursor to vaccine design (a "theoretical approach"). In a new commentary, scientists from the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, offer a historical perspective on the search for a safe and effective HIV vaccine through the lens of these two vaccine development strategies, and describe how they influence current promising approaches in HIV vaccinology.
Numerous characteristics of HIV, such as its ability to evade the immune system, present unprecedented challenges for vaccine development. Many initially promising investigational HIV vaccines ultimately have proved ineffective in clinical trials, leading some researchers to question the utility of an empirical approach when fundamental questions about the virus remain unanswered. However, the research community was encouraged by results from the RV144 trial in Thailand, which provided the first signal of vaccine efficacy with a 31 percent reduction in infection among vaccine recipients. Today, new trials aim to replicate and improve on the RV144 results.
Concurrently, scientists pursuing a theoretical approach have made strides in characterizing powerful broadly neutralizing antibodies (bNAbs) that target many HIV strains and develop naturally over time in a minority of HIV-infected people. Scientists hope to design vaccine regimens that stimulate the immune systems of uninfected people to produce bNAbs. Recently, researchers have made progress toward this goal, for example, by developing a stable version of the HIV envelope trimer-the HIV surface protein that is a target of known bNAbs-that potentially could be used as an immune-stimulating vaccine component.
At the same time as bNAb-based research and other early stage approaches, such as T-cell-based vaccines, move from theory to design, research stemming from RV144 may improve on the modest efficacy seen in Thailand. "Ultimately, the theoretical and empirical approaches will coalesce, converging upon the effective vaccine so critically needed to end HIV transmission worldwide," the authors conclude.
AS Fauci and HD Marston. Toward an HIV vaccine: a scientific journey. Science. DOI: 10.1126/science.aac6300 (2015).
NIAID Director Anthony S. Fauci, M.D., is available for interviews.