What immune response should a vaccine elicit to prevent HIV infection? Two studies published online today bring scientists closer to answering this question by identifying previously unrecognized attributes of antibodies that appear to have reduced the risk of HIV infection in the only clinical trial to show efficacy, albeit modest, of an experimental vaccine regimen in people.
Earlier analyses of the results of that trial, known as RV144, suggested that antibodies to sites within a part of the HIV envelope called V1V2 correlated with reduced risk of HIV infection. These antibodies belong to a class called immunoglobulin G, or IgG. The new studies by two independent laboratories both found that only one subclass of V1V2-directed IgG antibodies--the IgG3 subclass--is associated with antiviral responses linked to the reduced risk of HIV infection seen in RV144. The experiments were led by Georgia D. Tomaras, Ph.D., of the Duke Human Vaccine Institute, and Galit Alter, Ph.D., of the Ragon Institute, with funding in part from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.
In the study led by Dr. Tomaras, scientists found that V1V2-specific IgG3 antibodies correlated with a decreased risk of infection in RV144 vaccinees and were linked to HIV-eliminating activity. The researchers also discovered that the level of V1V2-specific IgG3 antibodies in vaccinees' blood waned rapidly, as did the efficacy of the investigational vaccines tested in the RV144 trial (from 60 percent efficacy at 12 months post-vaccination to 31.2 percent efficacy at 42 months). The study led by Dr. Alter demonstrated that RV144 vaccination induced antibodies able to direct multiple, coordinated HIV-eliminating activities, and that these activities were conducted primarily by V1V2-specific IgG3 antibodies.
More research is needed to determine whether V1V2-directed IgG3 antibodies actually protected some vaccinees from HIV infection, as well as whether there was a relationship between the fast decline in IgG3 antibodies and the sharp drop in efficacy of the investigational RV144 vaccines. Information from the current and ongoing studies will help scientists refine their efforts to design and test HIV vaccines that build on the success of RV144.
AW Chung et al. Polyfunctional Fc-effector profiles mediated by IgG subclass selection distinguish RV144 and VAX003 vaccines. Science Translational Medicine DOI: 10.1126/scitranslmed.3007736 (2014).
NL Yates et al. Vaccine-induced Env V1-V2 IgG3 correlates with lower HIV-1 infection risk and declines soon after vaccination. Science Translational Medicine DOI: 10.1126/scitranslmed.3007730 (2014).
NIAID Director Anthony S. Fauci, M.D., is available for comment.
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