Potential immunomodulatory effects of CAS+IMD monoclonal antibody cocktail in hospitalized patients with COVID-19.

Autor:	Wang B; Regeneron Pharmaceuticals, Inc., Tarrytown, New York, NY, 10591, USA., Golubov J; Regeneron Pharmaceuticals, Inc., Tarrytown, New York, NY, 10591, USA., Oswald EM; Regeneron Pharmaceuticals, Inc., Tarrytown, New York, NY, 10591, USA., Poon P; Regeneron Pharmaceuticals, Inc., Tarrytown, New York, NY, 10591, USA., Wei Q; Regeneron Pharmaceuticals, Inc., Tarrytown, New York, NY, 10591, USA., Lett C; Regeneron Pharmaceuticals, Inc., Tarrytown, New York, NY, 10591, USA., Shehadeh F; Division of Infectious Diseases, Department of Medicine, The Brown Alpert Medical School and the Miriam Hospital, Providence, RI, USA; Department of Medicine, Houston Methodist Academic Institute, Houston, TX, 77030, USA., Kaczynski M; Division of Infectious Diseases, Department of Medicine, The Brown Alpert Medical School and the Miriam Hospital, Providence, RI, USA., Felix LO; Division of Infectious Diseases, Department of Medicine, The Brown Alpert Medical School and the Miriam Hospital, Providence, RI, USA; Department of Medicine, Houston Methodist Academic Institute, Houston, TX, 77030, USA., Mishra B; Division of Infectious Diseases, Department of Medicine, The Brown Alpert Medical School and the Miriam Hospital, Providence, RI, USA; Department of Medicine, Houston Methodist Academic Institute, Houston, TX, 77030, USA., Mylona EK; Division of Infectious Diseases, Department of Medicine, The Brown Alpert Medical School and the Miriam Hospital, Providence, RI, USA; Department of Medicine, Houston Methodist Academic Institute, Houston, TX, 77030, USA., Wipperman MF; Regeneron Pharmaceuticals, Inc., Tarrytown, New York, NY, 10591, USA., Chio E; Regeneron Pharmaceuticals, Inc., Tarrytown, New York, NY, 10591, USA., Hamon SC; Regeneron Pharmaceuticals, Inc., Tarrytown, New York, NY, 10591, USA., Hooper AT; Regeneron Pharmaceuticals, Inc., Tarrytown, New York, NY, 10591, USA., Somersan-Karakaya S; Regeneron Pharmaceuticals, Inc., Tarrytown, New York, NY, 10591, USA., Musser BJ; Regeneron Pharmaceuticals, Inc., Tarrytown, New York, NY, 10591, USA., Petro CD; Regeneron Pharmaceuticals, Inc., Tarrytown, New York, NY, 10591, USA., Hamilton JD; Regeneron Pharmaceuticals, Inc., Tarrytown, New York, NY, 10591, USA., Sleeman MA; Regeneron Pharmaceuticals, Inc., Tarrytown, New York, NY, 10591, USA., Kalliolias GD; Regeneron Pharmaceuticals, Inc., Tarrytown, New York, NY, 10591, USA., Mylonakis E; Division of Infectious Diseases, Department of Medicine, The Brown Alpert Medical School and the Miriam Hospital, Providence, RI, USA; Department of Medicine, Houston Methodist Academic Institute, Houston, TX, 77030, USA., Skokos D; Regeneron Pharmaceuticals, Inc., Tarrytown, New York, NY, 10591, USA. Electronic address: Dimitris.Skokos@regeneron.com.
Jazyk:	angličtina
Zdroj:	EBioMedicine [EBioMedicine] 2024 Oct; Vol. 108, pp. 105334. Date of Electronic Publication: 2024 Sep 12.
DOI:	10.1016/j.ebiom.2024.105334
Abstrakt:	Background: Passive administration of SARS-CoV-2 neutralizing monoclonal antibodies (mAbs), such as CAS + IMD (Casirivimab + Imdevimab) antibody cocktail demonstrated beneficial effects on clinical outcomes in hospitalized patients with COVID-19 who were seronegative at baseline and outpatients. However, little is known about their impact on the host immunophenotypes. Methods: We conducted an immunoprofiling study in 46 patients from a single site of a multi-site trial of CAS + IMD in hospitalized patients. We collected longitudinal samples during October 2020 ∼ April 2021, prior to the emergence of the Delta and Omicron variants and the use of COVID-19 vaccines. All collected samples were analyzed without exclusion and post-hoc statistical analysis was performed. We examined the dynamic interplay of CAS + IMD with host immunity applying dimensional reduction approach on plasma proteomics and high dimensional flow cytometry data. Findings: Using an unbiased clustering method, we identified unique immunophenotypes associated with acute inflammation and disease resolution. Compared to placebo group, administration of CAS + IMD accelerated the transition from an acute inflammatory immunophenotype, to a less inflammatory or "resolving" immunophenotype, as characterized by reduced tissue injury, proinflammatory markers and restored lymphocyte/monocyte imbalance independent of baseline serostatus. Moreover, CAS + IMD did not impair the magnitude or the quality of host T cell immunity against SARS-CoV-2 spike protein. Interpretation: Our results identified immunophenotypic changes indicative of a possible SARS-CoV-2 neutralizing antibodies-induced anti-inflammatory effect, without an evident impairment of cellular antiviral immunity, suggesting that further studies of Mabs effects on SAS-CoV-2 or other viral mediated inflammation are warranted. Funding: Regeneron Pharmaceuticals Inc and federal funds from the Department of Health and Human Services; Administration for Strategic Preparedness and Response; Biomedical Advanced Research and Development Authority, under OT number: HHSO100201700020C. Competing Interests: Declaration of interests B.W., J.G., P.P, Q.W., C.L., M.F.W., E.C., S.C.H., A.T.H., S.K., G.D.K., B.J.M., C.D.P., J.D.H., M.A.S., D.S. are employees of Regeneron Pharmaceuticals, Inc. E.M.O is former employee of Regeneron. E.M. (Eleftherios Mylonakis) received fundings from Regeneron Pharmaceuticals, SciClone Pharmaceuticals, Pfizer, Chemic Labs/KODA Therapeutics, Cidara, and Leidos Biomedical Research Inc./NCI, NIH/NIAID, NIH/NIGMS, and BARDA. (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze:	MEDLINE
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