Structural Basis for Broad HIV-1 Neutralization by the MPER-Specific Human Broadly Neutralizing Antibody LN01.

Published online

Journal Article

Potent and broadly neutralizing antibodies (bnAbs) are the hallmark of HIV-1 protection by vaccination. The membrane-proximal external region (MPER) of the HIV-1 gp41 fusion protein is targeted by the most broadly reactive HIV-1 neutralizing antibodies. Here, we examine the structural and molecular mechansims of neutralization by anti-MPER bnAb, LN01, which was isolated from lymph-node-derived germinal center B cells of an elite controller and exhibits broad neutralization breadth. LN01 engages both MPER and the transmembrane (TM) region, which together form a continuous helix in complex with LN01. The tilted TM orientation allows LN01 to interact simultaneously with the peptidic component of the MPER epitope and membrane via two specific lipid binding sites of the antibody paratope. Although LN01 carries a high load of somatic mutations, most key residues interacting with the MPER epitope and lipids are germline encoded, lending support for the LN01 epitope as a candidate for lineage-based vaccine development.

Full Text

Duke Authors

Cited Authors

  • Pinto, D; Fenwick, C; Caillat, C; Silacci, C; Guseva, S; Dehez, F; Chipot, C; Barbieri, S; Minola, A; Jarrossay, D; Tomaras, GD; Shen, X; Riva, A; Tarkowski, M; Schwartz, O; Bruel, T; Dufloo, J; Seaman, MS; Montefiori, DC; Lanzavecchia, A; Corti, D; Pantaleo, G; Weissenhorn, W

Published Date

  • October 22, 2019

Published In

PubMed ID

  • 31653484

Pubmed Central ID

  • 31653484

Electronic International Standard Serial Number (EISSN)

  • 1934-6069

Digital Object Identifier (DOI)

  • 10.1016/j.chom.2019.09.016

Language

  • eng

Conference Location

  • United States