Pietzsch, John Scheid, Johannes F. Mouquet, Hugo Klein, Florian Seaman, Michael S. Jankovic, Mila Corti, Davide Lanzavecchia, Antonio Nussenzweig, Michel C. 2010-08-02 The identification and characterization of conserved epitopes on the HIV-1 viral spike that are immunogenic in humans and targeted by neutralizing antibodies is an important step in vaccine design. Antibody cloning experiments revealed that 32% of all HIV-neutralizing antibodies expressed by the memory B cells in patients with high titers of broadly neutralizing antibodies recognize one or more “core” epitopes that were not defined. Here, we show that anti-core antibodies recognize a single conserved epitope on the gp120 subunit. Amino acids D474, M475, R476, which are essential for anti-core antibody binding, form an immunodominant triad at the outer domain/inner domain junction of gp120. The mutation of these residues to alanine impairs viral fusion and fitness. Thus, the core epitope, a frequent target of anti–HIV-neutralizing antibodies, including the broadly neutralizing antibody HJ16, is conserved and indispensible for viral infectivity. We conclude that the core epitope should be considered as a target for vaccine design. application/pdf https://susi.usi.ch/global/documents/319007 https://localhost:5000/ark:/12658/srd1319007 https://susi.usi.ch/documents/319007/files/Pietzsch_JEM_2010.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.1084/jem.20101176 info:eu-repo/semantics/altIdentifier/ark/12658/srd1319007 info:eu-repo/semantics/openAccess CC BY-NC-SA Journal of experimental medicine. - 2010, vol. 207, no. 9, p. 1995-2002 info:eu-repo/classification/udc/61 Human anti–HIV-neutralizing antibodies frequently target a conserved epitope essential for viral fitness http://purl.org/coar/resource_type/c_6501