HIV-1 Receptor Binding Site-Directed Antibodies Using a VH1-2 Gene Segment Orthologue Are Activated by Env Trimer Immunization

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The development of an HIV-1 vaccine that stimulates the production of antibodies capable of neutralizing diverse circulating HIV-1 strains remains a global priority. Studies have shown that broadly neutralizing antibodies (bNAbs) isolated from HIV-1 infected individuals can protect against infection in non-human primates and, in some cases, reduce viremia after already established infection. An intriguing feature of one class of bNAbs directed against the primary receptor binding site of HIV-1, the CD4 binding site (CD4bs), is that they are encoded by the same heavy chain gene segment, which encodes critical contacts for this class of Ab. Here, we asked if HIV-1 Env vaccination activates B cells that encode the rhesus macaque orthologue of this gene segment and if so what the genetic and structural properties of such antibodies are. We isolated a set of monoclonal antibodies encoded by this gene segment and demonstrate that one such Ab, GE356, binds the receptor binding site in a manner that is distinctly different from the mode of interaction of CD4bs-directed bNAbs. These results provide a possible explanation for the lack of broadly neutralizing activity following vaccination, even when antibodies encoded by gene segments frequently used in bNAbs are elicited.

Vyšlo v časopise: HIV-1 Receptor Binding Site-Directed Antibodies Using a VH1-2 Gene Segment Orthologue Are Activated by Env Trimer Immunization. PLoS Pathog 10(8): e32767. doi:10.1371/journal.ppat.1004337
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004337

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