Bamlanivimab therapy for acute COVID-19 does not blunt SARS-CoV-2–specific memory T cell responses

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Abstract

Despite the widespread use of SARS-CoV-2–specific monoclonal antibody (mAb) therapy for the treatment of acute COVID-19, the impact of this therapy on the development of SARS-CoV-2–specific T cell responses has been unknown, resulting in uncertainty as to whether anti–SARS-CoV-2 mAb administration may result in failure to generate immune memory. Alternatively, it has been suggested that SARS-CoV-2–specific mAb may enhance adaptive immunity to SARS-CoV-2 via a “vaccinal effect.” Bamlanivimab (Eli Lilly and Company) is a recombinant human IgG1 that was granted FDA emergency use authorization for the treatment of mild to moderate COVID-19 in those at high risk for progression to severe disease. Here, we compared SARS-CoV-2–specific CD4+ and CD8+ T cell responses of 95 individuals from the ACTIV-2/A5401 clinical trial 28 days after treatment with bamlanivimab versus placebo. SARS-CoV-2–specific T cell responses were evaluated using activation-induced marker assays in conjunction with intracellular cytokine staining. We demonstrate that most individuals with acute COVID-19 developed SARS-CoV-2–specific T cell responses. Overall, our findings suggest that the quantity and quality of SARS-CoV-2–specific T cell memory were not diminished in individuals who received bamlanivimab for acute COVID-19. Receipt of bamlanivimab during acute COVID-19 neither diminished nor enhanced SARS-CoV-2–specific cellular immunity.

Authors

Sydney I. Ramirez, Alba Grifoni, Daniela Weiskopf, Urvi M. Parikh, Amy Heaps, Farhoud Faraji, Scott F. Sieg, Justin Ritz, Carlee Moser, Joseph J. Eron, Judith S. Currier, Paul Klekotka, Alessandro Sette, David A. Wohl, Eric S. Daar, Michael D. Hughes, Kara W. Chew, Davey M. Smith, Shane Crotty, for the Accelerating COVID-19 Therapeutic Interventions and Vaccines–2/A5401 (ACTIV-2/A5401) Study Team