J Exp Med. 2010 Aug 30; 207(9):1995-2002.

PubMed ID: 20679402

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

Pietzsch J, Scheid JF, Mouquet H, Klein F, Seaman MS, Jankovic M, Corti D, Lanzavecchia A, Nussenzweig MC

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.