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Transient viral exposure drives functionally-coordinated humoral immune responses in HIV-1 post-treatment controllers

Luis Molinos-Albert 1 Valerie Lorin 1 Valérie Monceaux 2 Sylvie Orr 3 Asma Essat 3 Jérémy Dufloo 4 Olivier Schwartz 4 Christine Rouzioux 5 Laurence Meyer 3 Laurent Hocqueloux 6 Asier Sáez-Cirión 2 Hugo Mouquet 1, * Anrs Visconti Study Group Thierry Prazuck Barbara De Dieuleveult Firouzé Bani-Sadr 7 Maxime Hentzien 7 Jean-Luc Berger 7 Isabelle Kmiec 7 Gilles Pichancourt 8 Safa Nasri 8 Gilles Hittinger 9 Véronique Lambry 9 Anne-Cécile Beauey 9 Gilles Pialoux 10 Christia Palacios 10 Martin Siguier 10 Anne Adda 10 Jane Foucoin 10 Laurence Weiss 11 Marina Karmochkine 11 Mohamed Meghadecha 11 Magali Ptak 11 Dominique Salmon-Ceron 12 Philippe Blanche 12 Marie-Pierre Piétri 12 Jean-Michel Molina 13 Olivier Taulera 13 Caroline Lascoux-Combe 13 Diane Ponscarme 13 Jeannine Delgado Bertaut 13 Djamila Makhloufi 14 Matthieu Godinot 14 Valérie Artizzu 14 Yazdan Yazdanpanah 15 Sophie Matheron 15 Cindy Godard 15 Zélie Julia 15 Louis Bernard 15 Frédéric Bastides 16 Olivier Bourgault 16 Christine Jacomet 17 Emilie Goncalves 17 Agnès Meybeck 18 Thomas Huleux 18 Pauline Cornavin 18 Yasmine Debab 19 David Théron 19 Patrick Miailhes 20 Laurent Cotte 20 Sophie Pailhes 20 Stanislas Ogoudjobi 20 Jean Paul Viard 21 Marie-Josée Dulucq 21 Loïc Bodard 22 Francoise Churaqui 22 Thomas Guimard 23 Laetitia Laine 23
* Corresponding author
1 Immunologie humorale - Humoral Immunology
2 HIV, Inflammation et persistance - HIV, Inflammation and Persistence
3 CESP - Centre de recherche en épidémiologie et santé des populations
4 Virus et Immunité - Virus and immunity
5 Service de Microbiologie Clinique [Paris]
6 La Source Hospital-CHR
7 CHU Reims - Centre Hospitalier Universitaire de Reims
8 Centre Hospitalier Henri Duffaut (Avignon)
9 CHI de Toulon
10 CHU Tenon [AP-HP]
11 HEGP - Hôpital Européen Georges Pompidou [APHP]
12 Hôpital Cochin [AP-HP]
13 AP-HP - Hopital Saint-Louis [AP-HP]
14 Hôpital Edouard Herriot [CHU - HCL]
15 AP-HP - Hôpital Bichat - Claude Bernard [Paris]
16 Hôpital Bretonneau
17 CHU Gabriel Montpied [Clermont-Ferrand]
18 Centre Hospitalier Gustave Dron [Tourcoing]
19 Hôpital Charles Nicolle [Rouen]
20 Hôpital de la Croix-Rousse [CHU - HCL]
21 Hôpital Hôtel-Dieu [Paris]
22 IMM - Institut mutualiste Monsouris
23 Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon
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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Submitted on : Thursday, April 28, 2022 - 2:37:37 PM
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PASTEUR | HCL | HEH | UVSQ | ANR | CNRS | UNIV-PARIS-SACLAY | UNIV-PARIS | SORBONNE-UNIVERSITE | SU-MEDECINE | SU-TI

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Luis Molinos-Albert, Valerie Lorin, Valérie Monceaux, Sylvie Orr, Asma Essat, et al.. Transient viral exposure drives functionally-coordinated humoral immune responses in HIV-1 post-treatment controllers. Nature Communications, Nature Publishing Group, 2022, 13 (1), pp.1944. ⟨10.1038/s41467-022-29511-1⟩. ⟨pasteur-03654232⟩

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