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

2022; Nature Portfolio; Volume: 13; Issue: 1 Linguagem: Inglês

10.1038/s41467-022-29511-1

2041-1723

Luis M. Molinos‐Albert, Valérie Lorin, Valérie Monceaux, Sylvie Orr, Asma Essat, Jérémy Dufloo, Olivier Schwartz, Christine Rouzioux, Laurence Meyer, Laurent Hocqueloux, Asier Sáez‐Cirión, Hugo Mouquet, Thiérry Prazuck, Barbara De Dieuleveult, Firouzé Bani‐Sadr, Maxime Hentzien, Jean‐Luc Berger, I Kmiec, Gilles Pichancourt, Safa Nasri, Gilles Hittinger, Véronique Lambry, Anne-Cécile Beauey, G. Pialoux, Christia Palacios, Martin Siguier, Anne Adda, J Foucoin, Laurence Weiss, Marina Karmochkine, Mohamed Meghadecha, Magali Ptak, Dominique Salmon‐Céron, P. Blanche, Marie‐Pierre Pietri, Jean‐Michel Molina, Olivier Tauléra, Caroline Lascoux‐Combe, Diane Ponscarme, Jeannine Delgado Bertaut, Djamila Makhloufi, Matthieu Godinot, Valérie Artizzu, Yazdan Yazdanpanah, Sophie Matheron, C. Godard, Zélie Julia, Louis Bernard, Frédéric Bastides, Olivier Bourgault, Christine Jacomet, Émilie 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, L Laine,

HIV/AIDS Research and Interventions

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.