Human anti–HIV-neutralizing antibodies frequently target a conserved epitope essential for viral fitness

Pietzsch, John; Scheid, Johannes F.; Mouquet, Hugo; Klein, Florian; Seaman, Michael S.; Jankovic, Mila; Corti, Davide; Lanzavecchia, Antonio; Nussenzweig, Michel C.

doi:10.1084/jem.20101176

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Journal article

Human anti–HIV-neutralizing antibodies frequently target a conserved epitope essential for viral fitness

Pietzsch, John Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065 - Institute of Chemistry and Biochemistry, Freie Universität Berlin, D-14195 Berlin, Germany
Scheid, Johannes F. Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065 - Charité Universitätsmedizin, D-10117 Berlin, Germany
Mouquet, Hugo Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065
Klein, Florian Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065
Seaman, Michael S. Beth Israel Deaconess Medical Center, Boston, MA 02215
Jankovic, Mila Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065
Corti, Davide Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Lanzavecchia, Antonio Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Nussenzweig, Michel C. Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065 - Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065

02.08.2010

Published in:

Journal of experimental medicine. - 2010, vol. 207, no. 9, p. 1995-2002

English 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.

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