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

Publication ,  Journal Article
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 ...
Published in: Nat Commun
August 3, 2022

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.

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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

August 3, 2022

Volume

13

Issue

1

Start / End Page

4515

Location

England

Related Subject Headings

  • Humans
  • HIV-1
  • HIV Infections
  • HIV Antibodies
  • Glycoproteins
  • Cryoelectron Microscopy
  • Complementarity Determining Regions
  • CD4 Antigens
  • Broadly Neutralizing Antibodies
  • Binding Sites
 

Citation

APA
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van Schooten, J., Farokhi, E., Schorcht, A., van den Kerkhof, T. L. G. M., Gao, H., van der Woude, P., … van Gils, M. J. (2022). Identification of IOMA-class neutralizing antibodies targeting the CD4-binding site on the HIV-1 envelope glycoprotein. Nat Commun, 13(1), 4515. https://doi.org/10.1038/s41467-022-32208-0
Schooten, Jelle van, Elinaz Farokhi, Anna Schorcht, Tom L. G. M. van den Kerkhof, Hongmei Gao, Patricia van der Woude, Judith A. Burger, et al. “Identification of IOMA-class neutralizing antibodies targeting the CD4-binding site on the HIV-1 envelope glycoprotein.Nat Commun 13, no. 1 (August 3, 2022): 4515. https://doi.org/10.1038/s41467-022-32208-0.
van Schooten J, Farokhi E, Schorcht A, van den Kerkhof TLGM, Gao H, van der Woude P, et al. Identification of IOMA-class neutralizing antibodies targeting the CD4-binding site on the HIV-1 envelope glycoprotein. Nat Commun. 2022 Aug 3;13(1):4515.
van Schooten, Jelle, et al. “Identification of IOMA-class neutralizing antibodies targeting the CD4-binding site on the HIV-1 envelope glycoprotein.Nat Commun, vol. 13, no. 1, Aug. 2022, p. 4515. Pubmed, doi:10.1038/s41467-022-32208-0.
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. Identification of IOMA-class neutralizing antibodies targeting the CD4-binding site on the HIV-1 envelope glycoprotein. Nat Commun. 2022 Aug 3;13(1):4515.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

August 3, 2022

Volume

13

Issue

1

Start / End Page

4515

Location

England

Related Subject Headings

  • Humans
  • HIV-1
  • HIV Infections
  • HIV Antibodies
  • Glycoproteins
  • Cryoelectron Microscopy
  • Complementarity Determining Regions
  • CD4 Antigens
  • Broadly Neutralizing Antibodies
  • Binding Sites