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
Show more…
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.
-
Language
-
-
Classification
-
Medicine
-
License
-
License undefined
-
Identifiers
-
-
Persistent URL
-
https://n2t.net/ark:/12658/srd1319007
Statistics
Document views: 43
File downloads:
- Pietzsch_JEM_2010.pdf: 133