Following HIV infection, most people make antibodies to the envelope glycoprotein, yet only a few make broadly neutralizing antibodies that target conserved antigenic sites on the envelope glycoprotein. Past research efforts to immunize with envelope glycoproteins failed because the vaccine glycoproteins failed to elicit broadly neutralizing antibodies. The resulting antibodies were specific for unique epitopes on the HIV strain of the vaccine glycoprotein protein, rather than conserved epitopes that can elicit broad protection against multiple HIV strains in circulation. HIV viruses evade antibodies by sterically concealing important neutralizing determinants such as, the CD4 binding site (CD4BS) on gp120. The induction of broadly neutralizing antibodies by immunization remains a major challenge of HIV vaccine research.
FDA researchers developed immunogenic gp120 polypeptides with targeted amino acid deletions to expose the CD4 binding site (CD4BS), reducing the conformational barrier to the CD4BS binding site. The variant immunogenic polypeptides enabled improved monoclonal antibody binding to CD4BS and elicited antibodies to the CD4BS. Modified forms of gp120, in which the CD4 binding site is more exposed and accessible to antibodies, may provide a novel epitope for eliciting broadly neutralizing antibodies to the CD4BS.
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Development Stage: immunogenicity studies in rhesus macaques
Inventors: Ira Berkower
“Targeted deletion in the beta20-beta21 loop of HIV envelope glycoprotein gp120 exposes the CD4 binding site for antibody binding. Virology 2008 Aug 1;377(2):330-338. PMID: 18519142
US Patent No. 8,628,782 issued 01.14.2014
US Patent No. 9,266,928 issued 02.23.2016
Product Area: Biologics, Vaccines, Diagnostics
FDA Reference No: E-2008-027
Bill Ronnenberg, MS, JD/MIP
FDA Technology Transfer Program