Identification of IOMA-class neutralizing antibodies targeting the CD4-binding site on the HIV-1 envelope glycoprotein.

Journal Article (Journal Article)

A major goal of current HIV-1 vaccine design efforts is to induce broadly neutralizing antibodies (bNAbs). The VH1-2-derived bNAb IOMA directed to the CD4-binding site of the HIV-1 envelope glycoprotein is of interest because, unlike the better-known VH1-2-derived VRC01-class bNAbs, it does not require a rare short light chain complementarity-determining region 3 (CDRL3). Here, we describe three IOMA-class NAbs, ACS101-103, with up to 37% breadth, that share many characteristics with IOMA, including an average-length CDRL3. Cryo-electron microscopy revealed that ACS101 shares interactions with those observed with other VH1-2 and VH1-46-class bNAbs, but exhibits a unique binding mode to residues in loop D. Analysis of longitudinal sequences from the patient suggests that a transmitter/founder-virus lacking the N276 glycan might have initiated the development of these NAbs. Together these data strengthen the rationale for germline-targeting vaccination strategies to induce IOMA-class bNAbs and provide a wealth of sequence and structural information to support such strategies.

Full Text

Duke Authors

Cited Authors

  • van Schooten, J; Farokhi, E; Schorcht, A; van den Kerkhof, TLGM; Gao, H; van der Woude, P; Burger, JA; Meesters, TGR; Bijl, T; Ghalaiyini, R; Turner, HL; Dorning, J; van Schaik, BDC; van Kampen, AHC; Labranche, CC; Stanfield, RL; Sok, D; Montefiori, DC; Burton, DR; Seaman, MS; Ozorowski, G; Wilson, IA; Sanders, RW; Ward, AB; van Gils, MJ

Published Date

  • August 3, 2022

Published In

Volume / Issue

  • 13 / 1

Start / End Page

  • 4515 -

PubMed ID

  • 35922441

Pubmed Central ID

  • PMC9349188

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/s41467-022-32208-0

Language

  • eng

Conference Location

  • England