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

• Published in: Nature communications Vol. 13; no. 1; p. 6473
• Main Authors: Rosás-Umbert, Miriam, Gunst, Jesper D., Pahus, Marie H., Olesen, Rikke, Schleimann, Mariane, Denton, Paul W., Ramos, Victor, Ward, Adam, Kinloch, Natalie N., Copertino, Dennis C., Escribà, Tuixent, Llano, Anuska, Brumme, Zabrina L., Brad Jones, R., Mothe, Beatriz, Brander, Christian, Fox, Julie, Nussenzweig, Michel C., Fidler, Sarah, Caskey, Marina, Tolstrup, Martin, Søgaard, Ole S.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 29.10.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/1; 13/21; 13/31; 631/250/255/1901; 692/308/575; Animals; Antibodies; Antibodies, Neutralizing; Antiretroviral therapy; Antiviral agents; Broadly Neutralizing Antibodies; CD8 antigen; CD8-Positive T-Lymphocytes; Cell-mediated immunity; Gag protein; HIV; HIV Antibodies; HIV Infections; HIV-1; Human immunodeficiency virus; Humanities and Social Sciences; Humans; Immunity; Interferon; Interferon-gamma; Lymphocytes; Lymphocytes T; Macaca mulatta; multidisciplinary; Neutralizing; Primates; Science; Science (multidisciplinary); Simian Acquired Immunodeficiency Syndrome; Simian Immunodeficiency Virus; γ-Interferon
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-34171-2

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. Broadly neutralising anti-HIV-1 antibody (bNAb) administration in nonhuman primates has been shown to stimulate adaptive T cell-specific immunity, with infection prevention observed. In this work, the authors longitudinally analyse HIV-1 specific cellular immunity in HIV-1- infected individuals starting ART with or without adjunctive bNAb treatment.