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

TitleHuman anti-HIV-neutralizing antibodies frequently target a conserved epitope essential for viral fitness.
Publication TypeJournal Article
Year of Publication2010
AuthorsPietzsch J, Scheid JF, Mouquet H, Klein F, Seaman MS, Jankovic M, Corti D, Lanzavecchia A, Nussenzweig MC
JournalJ Exp Med
Volume207
Issue9
Pagination1995-2002
Date Published2010 Aug 30
ISSN1540-9538
KeywordsAntibodies, Neutralizing, B-Lymphocytes, Cell Line, Epitopes, Herpesvirus 4, Human, HIV Antibodies, HIV Envelope Protein gp120, HIV-1, Humans, Models, Molecular, Mutation, Protein Binding, Protein Structure, Tertiary
Abstract

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.

DOI10.1084/jem.20101176
Alternate JournalJ. Exp. Med.
PubMed ID20679402