HIV-Specific B Cell Frequency Correlates with Neutralization Breadth in Patients Naturally Controlling HIV-Infection

HIV-specific broadly neutralizing antibodies (bnAbs) have been isolated from patients with high viremia but also from HIV controllers that repress HIV-1 replication. In these elite controllers (ECs), multiple parameters contribute to viral suppression, including genetic factors and immune responses....

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Main Authors: Angeline Rouers, Jéromine Klingler, Bin Su, Assia Samri, Géraldine Laumond, Sophie Even, Véronique Avettand-Fenoel, Clemence Richetta, Nicodème Paul, Faroudy Boufassa, Laurent Hocqueloux, Hugo Mouquet, Christine Rouzioux, Olivier Lambotte, Brigitte Autran, Stéphanie Graff-Dubois, Christiane Moog, Arnaud Moris
Format: Article
Language:English
Published: Elsevier 2017-07-01
Series:EBioMedicine
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S235239641730227X
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author Angeline Rouers
Jéromine Klingler
Bin Su
Assia Samri
Géraldine Laumond
Sophie Even
Véronique Avettand-Fenoel
Clemence Richetta
Nicodème Paul
Faroudy Boufassa
Laurent Hocqueloux
Hugo Mouquet
Christine Rouzioux
Olivier Lambotte
Brigitte Autran
Stéphanie Graff-Dubois
Christiane Moog
Arnaud Moris
author_facet Angeline Rouers
Jéromine Klingler
Bin Su
Assia Samri
Géraldine Laumond
Sophie Even
Véronique Avettand-Fenoel
Clemence Richetta
Nicodème Paul
Faroudy Boufassa
Laurent Hocqueloux
Hugo Mouquet
Christine Rouzioux
Olivier Lambotte
Brigitte Autran
Stéphanie Graff-Dubois
Christiane Moog
Arnaud Moris
author_sort Angeline Rouers
collection DOAJ
description HIV-specific broadly neutralizing antibodies (bnAbs) have been isolated from patients with high viremia but also from HIV controllers that repress HIV-1 replication. In these elite controllers (ECs), multiple parameters contribute to viral suppression, including genetic factors and immune responses. Defining the immune correlates associated with the generation of bnAbs may help in designing efficient immunotherapies. In this study, in ECs either positive or negative for the HLA-B*57 protective allele, in treated HIV-infected and HIV-negative individuals, we characterized memory B cell compartments and HIV-specific memory B cells responses using flow cytometry and ELISPOT. ECs preserved their memory B cell compartments and in contrast to treated patients, maintained detectable HIV-specific memory B cell responses. All ECs presented IgG1+ HIV-specific memory B cells but some individuals also preserved IgG2+ or IgG3+ responses. Importantly, we also analyzed the capacity of sera from ECs to neutralize a panel of HIV strains including transmitted/founder virus. 29% and 21% of HLA-B*57+ and HLA-B*57− ECs, respectively, neutralized at least 40% of the viral strains tested. Remarkably, in HLA-B*57+ ECs the frequency of HIV-Env-specific memory B cells correlated positively with the neutralization breadth suggesting that preservation of HIV-specific memory B cells might contribute to the neutralizing responses in these patients.
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spelling doaj.art-99d391715fef461a87873d694db660882022-12-21T17:44:50ZengElsevierEBioMedicine2352-39642017-07-0121C15816910.1016/j.ebiom.2017.05.029HIV-Specific B Cell Frequency Correlates with Neutralization Breadth in Patients Naturally Controlling HIV-InfectionAngeline Rouers0Jéromine Klingler1Bin Su2Assia Samri3Géraldine Laumond4Sophie Even5Véronique Avettand-Fenoel6Clemence Richetta7Nicodème Paul8Faroudy Boufassa9Laurent Hocqueloux10Hugo Mouquet11Christine Rouzioux12Olivier Lambotte13Brigitte Autran14Stéphanie Graff-Dubois15Christiane Moog16Arnaud Moris17Sorbonne Universités, UPMC Univ Paris 06, INSERM U1135, CNRS ERL 8255, Center for Immunology and Microbial Infections – CIMI-Paris, Paris, FranceINSERM UMR_S 1109, Centre de Recherche en Immunologie et Hématologie, Faculté de Médecine, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, FranceINSERM UMR_S 1109, Centre de Recherche en Immunologie et Hématologie, Faculté de Médecine, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, FranceSorbonne Universités, UPMC Univ Paris 06, INSERM U1135, Center for Immunology and Microbial Infections – CIMI-Paris, Paris, FranceINSERM UMR_S 1109, Centre de Recherche en Immunologie et Hématologie, Faculté de Médecine, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, FranceSorbonne Universités, UPMC Univ Paris 06, INSERM U1135, Center for Immunology and Microbial Infections – CIMI-Paris, Paris, FranceEA7327, Univ Paris Descartes, Sorbonne Paris-Cité, Faculté de Médecine, Paris, FranceSorbonne Universités, UPMC Univ Paris 06, INSERM U1135, CNRS ERL 8255, Center for Immunology and Microbial Infections – CIMI-Paris, Paris, FranceINSERM UMR_S 1109, Centre de Recherche en Immunologie et Hématologie, Faculté de Médecine, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, FranceINSERM, U1018, Faculté de Médecine Paris Sud, Le Kremlin-Bicêtre, FranceService des Maladies Infectieuses Tropicales, Centre Hospitalier Régional, Orléans, FranceLaboratory of Humoral Response to Pathogens, Department of Immunology, Institut Pasteur, Paris, FranceEA7327, Univ Paris Descartes, Sorbonne Paris-Cité, Faculté de Médecine, Paris, FranceUniversité Paris Sud, Le Kremin Bicêtre, FranceSorbonne Universités, UPMC Univ Paris 06, INSERM U1135, Center for Immunology and Microbial Infections – CIMI-Paris, Paris, FranceSorbonne Universités, UPMC Univ Paris 06, INSERM U1135, CNRS ERL 8255, Center for Immunology and Microbial Infections – CIMI-Paris, Paris, FranceINSERM UMR_S 1109, Centre de Recherche en Immunologie et Hématologie, Faculté de Médecine, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, FranceSorbonne Universités, UPMC Univ Paris 06, INSERM U1135, CNRS ERL 8255, Center for Immunology and Microbial Infections – CIMI-Paris, Paris, FranceHIV-specific broadly neutralizing antibodies (bnAbs) have been isolated from patients with high viremia but also from HIV controllers that repress HIV-1 replication. In these elite controllers (ECs), multiple parameters contribute to viral suppression, including genetic factors and immune responses. Defining the immune correlates associated with the generation of bnAbs may help in designing efficient immunotherapies. In this study, in ECs either positive or negative for the HLA-B*57 protective allele, in treated HIV-infected and HIV-negative individuals, we characterized memory B cell compartments and HIV-specific memory B cells responses using flow cytometry and ELISPOT. ECs preserved their memory B cell compartments and in contrast to treated patients, maintained detectable HIV-specific memory B cell responses. All ECs presented IgG1+ HIV-specific memory B cells but some individuals also preserved IgG2+ or IgG3+ responses. Importantly, we also analyzed the capacity of sera from ECs to neutralize a panel of HIV strains including transmitted/founder virus. 29% and 21% of HLA-B*57+ and HLA-B*57− ECs, respectively, neutralized at least 40% of the viral strains tested. Remarkably, in HLA-B*57+ ECs the frequency of HIV-Env-specific memory B cells correlated positively with the neutralization breadth suggesting that preservation of HIV-specific memory B cells might contribute to the neutralizing responses in these patients.http://www.sciencedirect.com/science/article/pii/S235239641730227XHIVElite controllersMemory B cellsB cell-ELISPOTNeutralizationTier-2 virusIgG
spellingShingle Angeline Rouers
Jéromine Klingler
Bin Su
Assia Samri
Géraldine Laumond
Sophie Even
Véronique Avettand-Fenoel
Clemence Richetta
Nicodème Paul
Faroudy Boufassa
Laurent Hocqueloux
Hugo Mouquet
Christine Rouzioux
Olivier Lambotte
Brigitte Autran
Stéphanie Graff-Dubois
Christiane Moog
Arnaud Moris
HIV-Specific B Cell Frequency Correlates with Neutralization Breadth in Patients Naturally Controlling HIV-Infection
EBioMedicine
HIV
Elite controllers
Memory B cells
B cell-ELISPOT
Neutralization
Tier-2 virus
IgG
title HIV-Specific B Cell Frequency Correlates with Neutralization Breadth in Patients Naturally Controlling HIV-Infection
title_full HIV-Specific B Cell Frequency Correlates with Neutralization Breadth in Patients Naturally Controlling HIV-Infection
title_fullStr HIV-Specific B Cell Frequency Correlates with Neutralization Breadth in Patients Naturally Controlling HIV-Infection
title_full_unstemmed HIV-Specific B Cell Frequency Correlates with Neutralization Breadth in Patients Naturally Controlling HIV-Infection
title_short HIV-Specific B Cell Frequency Correlates with Neutralization Breadth in Patients Naturally Controlling HIV-Infection
title_sort hiv specific b cell frequency correlates with neutralization breadth in patients naturally controlling hiv infection
topic HIV
Elite controllers
Memory B cells
B cell-ELISPOT
Neutralization
Tier-2 virus
IgG
url http://www.sciencedirect.com/science/article/pii/S235239641730227X
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