TY - JOUR
T1 - Epitope convergence of broadly HIV-1 neutralizing IgA and IgG antibody lineages in a viremic controller
AU - Lorin, Valérie
AU - Fernández, Ignacio
AU - Masse-Ranson, Guillemette
AU - Bouvin-Pley, M. lanie
AU - Molinos-Albert, Luis M.
AU - Planchais, Cyril
AU - Hieu, Thierry
AU - Péhau-Arnaudet, G. rard
AU - Hrebík, Dominik
AU - Girelli-Zubani, Giulia
AU - Fiquet, Oriane
AU - Guivel-Benhassine, Florence
AU - Sanders, Rogier W.
AU - Walker, Bruce D.
AU - Schwartz, Olivier
AU - Scheid, Johannes F.
AU - Dimitrov, Jordan D.
AU - Plevka, Pavel
AU - Braibant, Martine
AU - Seaman, Michael S.
AU - Bontems, François
AU - di Santo, James P.
AU - Rey, F. lix A.
AU - Mouquet, Hugo
N1 - Funding Information:
The NanoImaging Core was created with the help of a grant from the French Government’s Investissements d’Avenir program (EQUIPEX CACSICE - Centre d’analyse de systèmes complexes dans les environnements complexes, ANR-11-EQPX-0008). We thank the NIH AIDS Reagent Program (Division of AIDS, National Institute of Allergy and Infectious Diseases, NIH) for contributing to reagents and the Agence National de Recherche sur le SIDA et les hépatites virales (ANRS) for an equipment grant support. The Biomics platform is supported by France Génomique (ANR-10-INBS-09-09) and IBISA. I. Fernández and C. Planchais were recipients of an ANRS postdoctoral fellowship. The J.P. Di Santo laboratory received support from the Vaccine Research Institute (Créteil, France). H. Mouquet received core grants from the Institut Pasteur, Institut national de la santé et de la recherche médicale, and the Milieu Intérieur Program (ANR-10-LABX-69-01). This work was supported by the European Research Council Seventh Framework Program (ERC-2013-StG 337146), and by Gilead Sciences HIV Cure Grants (#00397).
Funding Information:
We are grateful to all participants who consented to be part of this study. We thank Arlene M. Hurley (the Rockefeller University Hospital) and Nathalie Jolly from the clinical core of the Center for Translational Sciences (Institut Pasteur) for their assistance on the preparation of the BHUANTIVIH protocol, Sandrine Schmutz and Sophie Novault (Unit? de Technologie et Service-Cytom?trie et Biomarqueurs, Institut Pasteur) for their help with single-cell sorting, and Laurence Ma (Biomics Plat-form, Institut Pasteur) for Illumina sequencing. We thank Na-talia T. Freund (Tel Aviv University) for kindly providing BG8/ BG18 expression vectors and Rogier W. Sanders (University of Amsterdam) and John P. Moore (Weill Medical College of Cornell University) for kindly providing BG505 SOSIP.664 expression vectors. We also thank the Core Facility Cryo-electron Microscopy and Tomography of Central European Institute of Technology Masaryk University for the initial support to the project, and the NanoImaging Core at Institut Pasteur for support with sample preparation and image acquisition of the data presented in this paper. The NanoImaging Core was created with the help of a grant from the French Government?s Investissements d?Avenir program (EQUIPEX CACSICE-Centre d?analyse de syst?mes complexes dans les environnements complexes, ANR-11-EQPX-0008). We thank the NIH AIDS Reagent Program (Division of AIDS, National Institute of Allergy and Infectious Diseases, NIH) for contributing to reagents and the Agence National de Re-cherche sur le SIDA et les h?patites virales (ANRS) for an equipment grant support. The Biomics platform is supported by France G?nomique (ANR-10-INBS-09-09) and IBISA. I. Fern?ndez and C. Planchais were recipients of an ANRS postdoctoral fel-lowship. The J.P. Di Santo laboratory received support from the Vaccine Research Institute (Cr?teil, France). H. Mouquet received core grants from the Institut Pasteur, Institut national de la sant? et de la recherche m?dicale, and the Milieu Int?rieur Program (ANR-10-LABX-69-01). This work was supported by the European Research Council Seventh Framework Program (ERC-2013-StG 337146), and by Gilead Sciences HIV Cure Grants (#00397).
Publisher Copyright:
© 2022 Lorin et al.
PY - 2022/3/7
Y1 - 2022/3/7
N2 - Decrypting the B cell ontogeny of HIV-1 broadly neutralizing antibodies (bNAbs) is paramount for vaccine design. Here, we characterized IgA and IgG bNAbs of three distinct B cell lineages in a viremic controller, two of which comprised only IgG+ or IgA+ blood memory B cells; the third combined both IgG and IgA clonal variants. 7-269 bNAb in the IgA-only lineage displayed the highest neutralizing capacity despite limited somatic mutation, and delayed viral rebound in humanized mice. bNAbs in all three lineages targeted the N332 glycan supersite. The 2.8-Å resolution cryo-EM structure of 7-269-BG505 SOSIP.664 complex showed a similar pose as 2G12, on an epitope mainly composed of sugar residues comprising the N332 and N295 glycans. Binding and cryo-EM structural analyses showed that antibodies from the two other lineages interact mostly with glycans N332 and N386. Hence, multiple B cell lineages of IgG and IgA bNAbs focused on a unique HIV-1 site of vulnerability can codevelop in HIV-1 viremic controllers.
AB - Decrypting the B cell ontogeny of HIV-1 broadly neutralizing antibodies (bNAbs) is paramount for vaccine design. Here, we characterized IgA and IgG bNAbs of three distinct B cell lineages in a viremic controller, two of which comprised only IgG+ or IgA+ blood memory B cells; the third combined both IgG and IgA clonal variants. 7-269 bNAb in the IgA-only lineage displayed the highest neutralizing capacity despite limited somatic mutation, and delayed viral rebound in humanized mice. bNAbs in all three lineages targeted the N332 glycan supersite. The 2.8-Å resolution cryo-EM structure of 7-269-BG505 SOSIP.664 complex showed a similar pose as 2G12, on an epitope mainly composed of sugar residues comprising the N332 and N295 glycans. Binding and cryo-EM structural analyses showed that antibodies from the two other lineages interact mostly with glycans N332 and N386. Hence, multiple B cell lineages of IgG and IgA bNAbs focused on a unique HIV-1 site of vulnerability can codevelop in HIV-1 viremic controllers.
UR - https://www.scopus.com/pages/publications/85126474984
U2 - 10.1084/jem.20212045
DO - 10.1084/jem.20212045
M3 - Article
C2 - 35230385
SN - 0022-1007
VL - 219
JO - Journal of experimental medicine
JF - Journal of experimental medicine
IS - 3
M1 - e20212045
ER -
SDG 3 Good Health and Well-being