Research ArticleHIV

High-Resolution Definition of Vaccine-Elicited B Cell Responses Against the HIV Primary Receptor Binding Site

Science Translational Medicine  11 Jul 2012:
Vol. 4, Issue 142, pp. 142ra96
DOI: 10.1126/scitranslmed.3003752

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Neutralizing HIV

A successful vaccine elicits broadly neutralizing antibodies that bind to viruses and prevent infection, but achieving this feat has been a challenge in HIV vaccine development. A prime target for these antibodies is the HIV envelope glycoprotein Env, which binds to CD4 expressed on T cells, resulting in infection. The CD4 binding site on Env is highly conserved, and broadly reactive neutralizing antibodies have been found that selectively bind to this site in HIV-infected individuals. However, when Env is used as an immunogen, the antibodies elicited have only limited neutralization ability. Sundling et al. use a macaque model of HIV infection to tease apart the differences between the infection- and the vaccine-induced antibodies to the CD4 binding site of Env.

One limitation for HIV vaccine studies has been the lack of an animal model that mimics human disease. Sundling et al. found that the immunogenetics of the rhesus macaque immunoglobulin locus are similar to those of humans supporting the use of nonhuman primates for preclinical vaccine studies. The authors then immunized these macaques with Env and compared the elicited antibodies with known infection-induced antibodies targeting the CD4 binding site of HIV. They found that the vaccine-induced antibodies are different from broadly neutralizing infection-induced antibodies in the fine specificities targeted within the CD4 binding site as well as in the degree of somatic hypermutation. However, the vaccine-induced antibodies are not very different from non-broadly neutralizing, infection-induced antibodies. These results provide direction for researchers seeking to develop effective HIV vaccine candidates.