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)

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 CNRS-UMR3569 - 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 CHD Vendée - Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon

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.

Domains: Virology

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, 2022, 13 (1), pp.1944. ⟨10.1038/s41467-022-29511-1⟩. ⟨pasteur-03654232⟩