Evaluation of a panel of therapeutic antibody clinical candidates for efficacy against SARS-CoV-2 in Syrian hamsters.

Autor: Cong Y; Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Ft. Detrick, Frederick, MD, 21702, USA., Mucker EM; United States Army Medical Research Institute of Infectious Diseases, Ft. Detrick, Frederick, MD, 21702, USA., Perry DL; Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Ft. Detrick, Frederick, MD, 21702, USA., Dixit S; Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Ft. Detrick, Frederick, MD, 21702, USA., Kollins E; Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Ft. Detrick, Frederick, MD, 21702, USA., Byrum R; Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Ft. Detrick, Frederick, MD, 21702, USA., Huzella L; Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Ft. Detrick, Frederick, MD, 21702, USA., Kim R; United States Army Medical Research Institute of Infectious Diseases, Ft. Detrick, Frederick, MD, 21702, USA., Josleyn M; United States Army Medical Research Institute of Infectious Diseases, Ft. Detrick, Frederick, MD, 21702, USA., Kwilas S; United States Army Medical Research Institute of Infectious Diseases, Ft. Detrick, Frederick, MD, 21702, USA., Stefan C; United States Army Medical Research Institute of Infectious Diseases, Ft. Detrick, Frederick, MD, 21702, USA., Shoemaker CJ; United States Army Medical Research Institute of Infectious Diseases, Ft. Detrick, Frederick, MD, 21702, USA., Koehler J; United States Army Medical Research Institute of Infectious Diseases, Ft. Detrick, Frederick, MD, 21702, USA., Coyne S; United States Army Medical Research Institute of Infectious Diseases, Ft. Detrick, Frederick, MD, 21702, USA., Delp K; United States Army Medical Research Institute of Infectious Diseases, Ft. Detrick, Frederick, MD, 21702, USA., Liang J; Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Ft. Detrick, Frederick, MD, 21702, USA., Drawbaugh D; Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Ft. Detrick, Frederick, MD, 21702, USA., Hischak A; Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Ft. Detrick, Frederick, MD, 21702, USA., Hart R; Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Ft. Detrick, Frederick, MD, 21702, USA., Postnikova E; Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Ft. Detrick, Frederick, MD, 21702, USA., Vaughan N; Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Ft. Detrick, Frederick, MD, 21702, USA., Asher J; Leidos Supporting Department of Health and Human Services, Biomedical Advanced Research and Development Authority, Washington, DC, 20024, USA., St Claire M; Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Ft. Detrick, Frederick, MD, 21702, USA., Hanson J; United States Army Medical Research Institute of Infectious Diseases, Ft. Detrick, Frederick, MD, 21702, USA., Schmaljohn C; Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Ft. Detrick, Frederick, MD, 21702, USA., Eakin AE; Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, 20892, USA., Hooper JW; United States Army Medical Research Institute of Infectious Diseases, Ft. Detrick, Frederick, MD, 21702, USA., Holbrook MR; Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Ft. Detrick, Frederick, MD, 21702, USA. Electronic address: michael.holbrook@nih.gov.
Jazyk: angličtina
Zdroj: Antiviral research [Antiviral Res] 2023 May; Vol. 213, pp. 105589. Date of Electronic Publication: 2023 Mar 30.
DOI: 10.1016/j.antiviral.2023.105589
Abstrakt: The COVID-19 pandemic spurred the rapid development of a range of therapeutic antibody treatments. As part of the US government's COVID-19 therapeutic response, a research team was assembled to support assay and animal model development to assess activity for therapeutics candidates against SARS-CoV-2. Candidate treatments included monoclonal antibodies, antibody cocktails, and products derived from blood donated by convalescent patients. Sixteen candidate antibody products were obtained directly from manufacturers and evaluated for neutralization activity against the WA-01 isolate of SARS-CoV-2. Products were further tested in the Syrian hamster model using prophylactic (-24 h) or therapeutic (+8 h) treatment approaches relative to intranasal SARS-CoV-2 exposure. In vivo assessments included daily clinical scores and body weights. Viral RNA and viable virus titers were quantified in serum and lung tissue with histopathology performed at 3d and 7d post-virus-exposure. Sham-treated, virus-exposed hamsters showed consistent clinical signs with concomitant weight loss and had detectable viral RNA and viable virus in lung tissue. Histopathologically, interstitial pneumonia with consolidation was present. Therapeutic efficacy was identified in treated hamsters by the absence or diminution of clinical scores, body weight loss, viral loads, and improved semiquantitative lung histopathology scores. This work serves as a model for the rapid, systematic in vitro and in vivo assessment of the efficacy of candidate therapeutics at various stages of clinical development. These efforts provided preclinical efficacy data for therapeutic candidates. Furthermore, these studies were invaluable for the phenotypic characterization of SARS CoV-2 disease in hamsters and of utility to the broader scientific community.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Published by Elsevier B.V.)
Databáze: MEDLINE
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