Scientists Evaluate Immune Responses to Develop HIV Vaccine

Specific vaccine-induced immune responses correlate with reduced HIV infection.

A recent study revealed new information about the immune responses associated with protection from HIV infection.

The findings indicate new avenues for scientists to take in the effort to find an HIV vaccine. Results from the RV144 study from 2009 provided the first signal of HIV vaccine efficacy: a 31% reduction in infection among patients administered the vaccine.

Since that time, an international research consortium has been extensively researching molecular clues to explain why the vaccine showed this modest protective effect.

Findings from the review hint at the types of immune responses a preventive HIV vaccine may need to induce. The article was co-authored by leaders in HIV vaccinology, including Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases and lead author Lawrence Corey, MD, of the Fred Hutchinson Cancer Research Center.

Analyses of participants in the previous trial indicated that specific vaccine-induced immune responses, including the production of certain antiviral antibodies and CD4+ T cell responses to HIV’s envelope, correlate with reduced HIV infection.

Many of those vaccinated in the trial produced antibodies in the immunoglobulin G (IgG) family that bind to sites within part of the HIV envelope called V1V2. 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 linked to a lack of protection against HIV infection. Evidence indicates that IgA may block the protective action of IgG.

More recently, studies in monkeys revealed that enhancing protective antibody activity may increase vaccine efficacy. Scientists relied on findings from human and monkey studies to improve upon the efficacy of the RV144 vaccine regimen.

Researchers are also investigating strategies to increase the magnitude and durability of vaccine-induced immune responses associated with protection from HIV infection, in addition to developing vaccines that 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 authors concluded.