A new review published in Science and Translational Medicine outlines findings that hint at the types of immune responses a preventive HIV vaccine may need to induce.
Results from the RV144 trial, reported in 2009, noted a 31% reduction in HIV infection among vaccinees. Since then, an international research consortium has been searching for molecular clues to explain why the vaccine showed this effect.
Lead researcher Lawrence Corey, MD, of the Fred Hutchinson Cancer Research Center and colleagues reported on an analyses of RV144 volunteers, which revealed that particular vaccine-induced immune responses, including production of certain antiviral antibodies and CD4+ T cell responses to HIV’s outer envelope, correlate with reduced HIV infection. Many RV144 vaccinees produced antibodies in the immunoglobulin G (IgG) family that bind to sites within part of the HIV envelope called V1V2, the researchers noted.
These antibodies were linked to protection against acquiring HIV. However, high levels of a different type of envelope-binding antibody belonging to the IgA family were associated with a lack of protection against HIV infection. Evidence suggests that IgA may block the protective action of IgG. Recently, monkey studies testing vaccine regimens different from those in RV144 have supported the notion that enhancing protective antibody activity may increase vaccine efficacy.
Guided by findings from human and monkey studies, the researchers are working to improve upon the efficacy of the RV144 vaccine regimen.
The researchers are investigating strategies to increase the magnitude and durability of vaccine-induced immune responses associated with protection from HIV infection, as well as developing vaccines to elicit production of antibodies that are broadly neutralizing against a variety of HIV strains.
As development of an effective HIV vaccine continues, efforts stemming from the modest success of the RV144 trial have “produced a momentum and series of immune targets that will hopefully lead to an effective global vaccine effort,” the researchers conclude.