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J Exp Med. 2010 Aug 30;207(9):1995-2002. doi: 10.1084/jem.20101176. Epub 2010 Aug 2.

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

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Laboratory of Molecular Immunology and Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA.


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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