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

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 and Hugo Mouquet ()
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Luis M. Molinos-Albert: Institut Pasteur, Université Paris Cité
Valérie Lorin: Institut Pasteur, Université Paris Cité
Valérie Monceaux: Institut Pasteur, Université Paris Cité
Sylvie Orr: Université Paris-Sud, Université Paris-Saclay, INSERM
Asma Essat: Université Paris-Sud, Université Paris-Saclay, INSERM
Jérémy Dufloo: Institut Pasteur, Université Paris Cité and CNRS UMR3569
Olivier Schwartz: Institut Pasteur, Université Paris Cité and CNRS UMR3569
Christine Rouzioux: Assistance Publique-Hôpitaux de Paris, Service de Microbiologie Clinique, Hôpital Necker-Enfants Malades
Laurence Meyer: Université Paris-Sud, Université Paris-Saclay, INSERM
Laurent Hocqueloux: Service des Maladies Infectieuses et Tropicales, CHR d’Orléans-La Source
Asier Sáez-Cirión: Institut Pasteur, Université Paris Cité
Hugo Mouquet: Institut Pasteur, Université Paris Cité

Nature Communications, 2022, vol. 13, issue 1, 1-17

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-29511-1

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