Administration of broadly neutralizing anti-HIV-1 antibodies at ART initiation maintains long-term CD8+ T cell immunity
Míriam Rosás-Umbert, Jesper Damsgaard Gunst, Marie H. Pahus, Rikke Olesen, Mariane Høgsbjerg Schleimann, Paul W. Denton, Víctor Ramos, Adam R. Ward, Natalie N. Kinloch, Dennis C. Copertino, Tuixent Escribà, Anuska Llano, Zabrina L. Brumme, R. Brad Jones, Beatriz Mothe, Christian Brander, Julie Fox, Michel C. Nussenzweig, Sarah Fidler, Marina Caskey, Martin Tolstrup, Ole S. Søgaard
Abstract
Abstract In simian-human immunodeficiency virus (SHIV)-infected non-human primates, broadly neutralizing antibodies (bNAbs) against the virus appear to stimulate T cell immunity. To determine whether this phenomenon also occurs in humans we measured HIV-1-specific cellular immunity longitudinally in individuals with HIV-1 starting antiviral therapy (ART) with or without adjunctive bNAb 3BNC117 treatment. Using the activation-induced marker (AIM) assay and interferon-γ release, we observe that frequencies of Pol- and Gag-specific CD8 + T cells, as well as Gag-induced interferon-γ responses, are significantly higher among individuals that received adjunctive 3BNC117 compared to ART-alone at 3 and 12 months after starting ART. The observed changes in cellular immunity were directly correlated to pre-treatment 3BNC117-sensitivity. Notably, increased HIV-1-specific immunity is associated with partial or complete ART-free virologic control during treatment interruption for up to 4 years. Our findings suggest that bNAb treatment at the time of ART initiation maintains HIV-1-specific CD8 + T cell responses that are associated with ART-free virologic control.