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

• DOI: 10.1038/s41467-022-29511-1
• Publication Date: 2022-04-11T10:04:18Z
• Authors: Luis M. Molinos-A...; Valérie Lorin; Valérie Monceaux; Sylvie Orr; Asma Essat; Jérémy Dufloo; Olivier Schwartz; Christine Rouzioux; Laurence Meyer; Laurent Hocqueloux; Asier Sáez-Cirión; Hugo Mouquet; ; Thierry Prazuck; Barbara De Dieule...; 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-...; Philippe Blanche; Marie-Pierre Piétri; Jean-Michel Molina; Olivier Taulera; Caroline Lascoux-...; Diane Ponscarme; Jeannine Delgado ...; 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
• Keywords: 0301 basic medicine; 570; MESH: Humans; MESH: Antibodies; Science; Q; Humoral; HIV Infections; MESH: HIV Infections; Antibodies, Neutralizing; Article; MESH: Antibodies, Neutralizing; Immunity, Humoral; MESH: HIV-1; 03 medical and health sciences; [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology; HIV-1; Humans; MESH: Immunity, Humoral; Viremia; MESH: Viremia; Neutralizing; MESH: Immunity

AbstractHIV-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.