Administration of broadly neutralizing anti-HIV-1 antibodies at ART initiation maintains long-term CD8+ T cell immunity

Miriam Rosás-Umbert, Jesper D. Gunst, Marie H. Pahus, Rikke Olesen, Mariane Schleimann, Paul W. Denton, Victor Ramos, Adam 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 and Ole S. Søgaard ()
Additional contact information
Miriam Rosás-Umbert: Aarhus University
Jesper D. Gunst: Aarhus University
Marie H. Pahus: Aarhus University
Rikke Olesen: Aarhus University
Mariane Schleimann: Aarhus University Hospital
Paul W. Denton: University of Nebraska at Omaha
Victor Ramos: The Rockefeller University
Adam Ward: Weill Cornell Medical College
Natalie N. Kinloch: Simon Fraser University
Dennis C. Copertino: Weill Cornell Medical College
Tuixent Escribà: IrsiCaixa, AIDS Research Institute, Institute for Health Science Research Germans Trias i Pujol (IGTP), Hospital Germans Trias I Pujol
Anuska Llano: IrsiCaixa, AIDS Research Institute, Institute for Health Science Research Germans Trias i Pujol (IGTP), Hospital Germans Trias I Pujol
Zabrina L. Brumme: Simon Fraser University
R. Brad Jones: Weill Cornell Medical College
Beatriz Mothe: IrsiCaixa, AIDS Research Institute, Institute for Health Science Research Germans Trias i Pujol (IGTP), Hospital Germans Trias I Pujol
Christian Brander: IrsiCaixa, AIDS Research Institute, Institute for Health Science Research Germans Trias i Pujol (IGTP), Hospital Germans Trias I Pujol
Julie Fox: Guys and St Thomas’ National Health Service Trust
Michel C. Nussenzweig: The Rockefeller University
Sarah Fidler: Imperial College London
Marina Caskey: The Rockefeller University
Martin Tolstrup: Aarhus University
Ole S. Søgaard: Aarhus University

Nature Communications, 2022, vol. 13, issue 1, 1-12

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.

Date: 2022
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DOI: 10.1038/s41467-022-34171-2

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