Recognition determinants of broadly neutralizing human antibodies against dengue viruses

Alexander Rouvinski, Pablo Guardado-Calvo, Giovanna Barba-Spaeth, Stéphane Duquerroy, Marie Christine Vaney, Carlos M. Kikuti, M. Erika Navarro Sanchez, Wanwisa Dejnirattisai, Wiyada Wongwiwat, Ahmed Haouz, Christine Girard-Blanc, Stéphane Petres, William E. Shepard, Philippe Desprès, Fernando Arenzana-Seisdedos, Philippe Dussart, Juthathip Mongkolsapaya, Gavin R. Screaton, Félix A. Rey

Research output: Contribution to journalReview articlepeer-review

269 Scopus citations

Abstract

Dengue disease is caused by four different flavivirus serotypes, which infect 390 million people yearly with 25% symptomatic cases and for which no licensed vaccine is available. Recent phase III vaccine trials showed partial protection, and in particular no protection for dengue virus serotype 2 (refs 3, 4). Structural studies so far have characterized only epitopes recognized by serotype-specific human antibodies. We recently isolated human antibodies potently neutralizing all four dengue virus serotypes. Here we describe the X-ray structures of four of these broadly neutralizing antibodies in complex with the envelope glycoprotein E from dengue virus serotype 2, revealing that the recognition determinants are at a serotype-invariant site at the E-dimer interface, including the exposed main chain of the E fusion loop and the two conserved glycan chains. This 'E-dimer-dependent epitope' is also the binding site for the viral glycoprotein prM during virus maturation in the secretory pathway of the infected cell, explaining its conservation across serotypes and highlighting an Achilles' heel of the virus with respect to antibody neutralization. These findings will be instrumental for devising novel immunogens to protect simultaneously against all four serotypes of dengue virus.

Original languageAmerican English
Pages (from-to)109-113
Number of pages5
JournalNature
Volume520
Issue number7545
DOIs
StatePublished - 2 Apr 2015
Externally publishedYes

Bibliographical note

Publisher Copyright:
©2015 Macmillan Publishers Limited. All rights reserved.

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