1. Transient viral exposure drives functionally-coordinated humoral immune responses in HIV-1 post-treatment controllers
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Molinos-Albert, Luis, Lorin, Valerie, Monceaux, Valérie, Orr, Sylvie, Essat, Asma, Dufloo, Jérémy, Schwartz, Olivier, Rouzioux, Christine, Meyer, Laurence, Hocqueloux, Laurent, Sáez-Cirión, Asier, Mouquet, Hugo, Group, Anrs Visconti Study, Prazuck, Thierry, Dieuleveult, Barbara De, Bani-Sadr, Firouzé, Hentzien, Maxime, Berger, Jean-Luc, Kmiec, Isabelle, Pichancourt, Gilles, Nasri, Safa, Hittinger, Gilles, Lambry, Véronique, Beauey, Anne-Cécile, Pialoux, Gilles, Palacios, Christia, Siguier, Martin, Adda, Anne, Foucoin, Jane, Weiss, Laurence, Karmochkine, Marina, Meghadecha, Mohamed, Ptak, Magali, Salmon-Ceron, Dominique, Blanche, Philippe, Piétri, Marie-Pierre, Molina, Jean-Michel, Taulera, Olivier, Lascoux-Combe, Caroline, Ponscarme, Diane, Bertaut, Jeannine Delgado, Makhloufi, Djamila, Godinot, Matthieu, Artizzu, Valérie, Yazdanpanah, Yazdan, Matheron, Sophie, Godard, Cindy, Julia, Zélie, Bernard, Louis, Bastides, Frédéric, Bourgault, Olivier, Jacomet, Christine, Goncalves, Emilie, Meybeck, Agnès, Huleux, Thomas, Cornavin, Pauline, Debab, Yasmine, Théron, David, Miailhes, Patrick, Cotte, Laurent, Pailhes, Sophie, Ogoudjobi, Stanislas, Viard, Jean Paul, Dulucq, Marie-Josée, Bodard, Loïc, Churaqui, Francoise, Guimard, Thomas, Laine, Laetitia, Immunologie humorale - Humoral Immunology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), HIV, Inflammation et persistance - HIV, Inflammation and Persistence, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Service de Microbiologie Clinique [Paris], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), La Source Hospital-CHR, Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Henri Duffaut (Avignon), CHI de Toulon, CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hopital Saint-Louis [AP-HP] (AP-HP), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Centre Hospitalier Gustave Dron [Tourcoing], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Hôpital de la Croix-Rousse [CHU - HCL], Hôpital Hôtel-Dieu [Paris], Institut mutualiste Monsouris (IMM), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), We thank the NIH AIDS Reagent Program (Division of AIDS, NIAID, NIH) for contributing to reagents and the Agence National de Recherche sur le SIDA et les hépatites virales (ANRS) for an equipment grant support (AO2013-2 #13553, H.M.). L.M. M-A. is the recipient of a postdoctoral fellowship from the Pasteur-Roux-Cantarini program (Institut Pasteur). H.M. received core grants from the Institut Pasteur, the INSERM and the Milieu Intérieur Program (ANR-10-LABX-69-01). This work was conducted in the context of the ANRS RHIVIERA consortium, and was supported by the ANRS and the NIH/NIAID (grant #: P01AI131365, H.M.)., ANRS VISCONTI Study Group Thierry Prazuck, Barbara De Dieuleveult, Firouzé Bani-Sadr, Maxime Hentzien, Jean-Luc Berger, Isabelle Kmiec, Gilles Pichancourt, Safa Nasri, Gilles Hittinger, Véronique Lambry, Anne-Cécile Beauey, Gilles Pialoux, Christia Palacios, Martin Siguier, Anne Adda, Jane Foucoin, Laurence Weiss, Marina Karmochkine, Mohamed Meghadecha, Magali Ptak, Dominique Salmon-Ceron, Philippe Blanche, Marie-Pierre Piétri, Jean-Michel Molina, Olivier Taulera, Caroline Lascoux-Combe, Diane Ponscarme, Jeannine Delgado Bertaut, Djamila Makhloufi, Matthieu Godinot, Valérie Artizzu, Yazdan Yazdanpanah, Sophie Matheron, Cindy Godard, Zélie Julia, Louis Bernard, Frédéric Bastides, Olivier Bourgault, Christine Jacomet, Emilie Goncalves, Agnès Meybeck, Thomas Huleux, Pauline Cornavin, Yasmine Debab, David Théron, Patrick Miailhes, Laurent Cotte, Sophie Pailhes, Stanislas Ogoudjobi, Jean Paul Viard, Marie-Josée Dulucq, Loïc Bodard, Francoise Churaqui, Thomas Guimard & Laetitia Laine, ANR-10-LABX-0069,MILIEU INTERIEUR,GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE(2010), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Institut Pasteur [Paris]-Université Paris Cité (UPC), Virus et Immunité - Virus and immunity, and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC)
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Multidisciplinary ,MESH: Humans ,General Physics and Astronomy ,HIV Infections ,General Chemistry ,MESH: HIV Infections ,Antibodies, Neutralizing ,General Biochemistry, Genetics and Molecular Biology ,Immunity, Humoral ,MESH: Antibodies, Neutralizing ,MESH: HIV-1 ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,HIV-1 ,Humans ,Viremia ,MESH: Immunity, Humoral ,MESH: Viremia - Abstract
HIV-1 post-treatment controllers are rare individuals controlling HIV-1 infection for years after antiretroviral therapy interruption. Identification of immune correlates of control in post-treatment controllers could aid in designing effective HIV-1 vaccine and remission strategies. Here, we perform comprehensive immunoprofiling of the humoral response to HIV-1 in long-term post-treatment controllers. Global multivariate analyses combining clinico-virological and humoral immune data reveal distinct profiles in post-treatment controllers experiencing transient viremic episodes off therapy compared to those stably aviremic. Virally-exposed post-treatment controllers display stronger HIV-1 humoral responses, and develop more frequently Env-specific memory B cells and cross-neutralizing antibodies. Both are linked to short viremic exposures, which are also accompanied by an increase in blood atypical memory B cells and activated subsets of circulating follicular helper T cells. Still, most humoral immune variables only correlate with Th2-like circulating follicular helper T cells. Thus, post-treatment controllers form a heterogeneous group with two distinct viral behaviours and associated immune signatures. Post-treatment controllers stably aviremic present “silent” humoral profiles, while those virally-exposed develop functionally robust HIV-specific B-cell and antibody responses, which may participate in controlling infection.
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- 2022