Epitope convergence of broadly HIV-1 neutralizing IgA and IgG antibody lineages in a viremic controller

Valérie Lorin; Ignacio Fernández; Guillemette Masse-Ranson; M. lanie Bouvin-Pley; Luis M. Molinos-Albert; Cyril Planchais; Thierry Hieu; G. rard Péhau-Arnaudet; Dominik Hrebík; Giulia Girelli-Zubani; Oriane Fiquet; Florence Guivel-Benhassine; Rogier W. Sanders; Bruce D. Walker; Olivier Schwartz; Johannes F. Scheid; Jordan D. Dimitrov; Pavel Plevka; Martine Braibant; Michael S. Seaman; François Bontems; James P. di Santo; F. lix A. Rey; Hugo Mouquet

doi:https://doi.org/10.1084/jem.20212045

Epitope convergence of broadly HIV-1 neutralizing IgA and IgG antibody lineages in a viremic controller

Valérie Lorin, Ignacio Fernández, Guillemette Masse-Ranson, M. lanie Bouvin-Pley, Luis M. Molinos-Albert, Cyril Planchais, Thierry Hieu, G. rard Péhau-Arnaudet, Dominik Hrebík, Giulia Girelli-Zubani, Oriane Fiquet, Florence Guivel-Benhassine, Rogier W. Sanders, Bruce D. Walker, Olivier Schwartz, Johannes F. Scheid, Jordan D. Dimitrov, Pavel Plevka, Martine Braibant, Michael S. SeamanFrançois Bontems, James P. di Santo, F. lix A. Rey, Hugo Mouquet

Research output: Contribution to journal › Article › Academic › peer-review

10 Citations (Scopus)

Abstract

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.

Original language	English
Article number	e20212045
Journal	Journal of Experimental Medicine
Volume	219
Issue number	3
DOIs	https://doi.org/10.1084/jem.20212045
Publication status	Published - 7 Mar 2022

Access to Document

https://doi.org/10.1084/jem.20212045

Cite this

Lorin, V., Fernández, I., Masse-Ranson, G., Bouvin-Pley, M. L., Molinos-Albert, L. M., Planchais, C., Hieu, T., Péhau-Arnaudet, G. R., Hrebík, D., Girelli-Zubani, G., Fiquet, O., Guivel-Benhassine, F., Sanders, R. W., Walker, B. D., Schwartz, O., Scheid, J. F., Dimitrov, J. D., Plevka, P., Braibant, M., ... Mouquet, H. (2022). Epitope convergence of broadly HIV-1 neutralizing IgA and IgG antibody lineages in a viremic controller. Journal of Experimental Medicine, 219(3), Article e20212045. https://doi.org/10.1084/jem.20212045

@article{893564d6d7074a358c86b35a398dd08a,

title = "Epitope convergence of broadly HIV-1 neutralizing IgA and IgG antibody lineages in a viremic controller",

abstract = "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-{\AA} 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.",

author = "Val{\'e}rie Lorin and Ignacio Fern{\'a}ndez and Guillemette Masse-Ranson and Bouvin-Pley, {M. lanie} and Molinos-Albert, {Luis M.} and Cyril Planchais and Thierry Hieu and P{\'e}hau-Arnaudet, {G. rard} and Dominik Hreb{\'i}k and Giulia Girelli-Zubani and Oriane Fiquet and Florence Guivel-Benhassine and Sanders, {Rogier W.} and Walker, {Bruce D.} and Olivier Schwartz and Scheid, {Johannes F.} and Dimitrov, {Jordan D.} and Pavel Plevka and Martine Braibant and Seaman, {Michael S.} and Fran{\c c}ois Bontems and {di Santo}, {James P.} and Rey, {F. lix A.} and Hugo Mouquet",

note = "Funding Information: The NanoImaging Core was created with the help of a grant from the French Government{\textquoteright}s Investissements d{\textquoteright}Avenir program (EQUIPEX CACSICE - Centre d{\textquoteright}analyse de syst{\`e}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 Recherche sur le SIDA et les h{\'e}patites virales (ANRS) for an equipment grant support. The Biomics platform is supported by France G{\'e}nomique (ANR-10-INBS-09-09) and IBISA. I. Fern{\'a}ndez and C. Planchais were recipients of an ANRS postdoctoral fellowship. The J.P. Di Santo laboratory received support from the Vaccine Research Institute (Cr{\'e}teil, France). H. Mouquet received core grants from the Institut Pasteur, Institut national de la sant{\'e} et de la recherche m{\'e}dicale, and the Milieu Int{\'e}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). 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: {\textcopyright} 2022 Lorin et al.",

year = "2022",

month = mar,

day = "7",

doi = "https://doi.org/10.1084/jem.20212045",

language = "English",

volume = "219",

journal = "Journal of Experimental Medicine",

issn = "0022-1007",

publisher = "Rockefeller University Press",

number = "3",

}

Lorin, V, Fernández, I, Masse-Ranson, G, Bouvin-Pley, ML, Molinos-Albert, LM, Planchais, C, Hieu, T, Péhau-Arnaudet, GR, Hrebík, D, Girelli-Zubani, G, Fiquet, O, Guivel-Benhassine, F, Sanders, RW, Walker, BD, Schwartz, O, Scheid, JF, Dimitrov, JD, Plevka, P, Braibant, M, Seaman, MS, Bontems, F, di Santo, JP, Rey, FLA & Mouquet, H 2022, 'Epitope convergence of broadly HIV-1 neutralizing IgA and IgG antibody lineages in a viremic controller', Journal of Experimental Medicine, vol. 219, no. 3, e20212045. https://doi.org/10.1084/jem.20212045

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 - http://www.scopus.com/inward/record.url?scp=85126474984&partnerID=8YFLogxK

U2 - https://doi.org/10.1084/jem.20212045

DO - https://doi.org/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 -

Epitope convergence of broadly HIV-1 neutralizing IgA and IgG antibody lineages in a viremic controller

Abstract

Access to Document

Other files and links

Cite this