An Engineered Antibody with Broad Protective Efficacy in Murine Models of SARS and COVID-19.

التفاصيل البيبلوغرافية
العنوان: An Engineered Antibody with Broad Protective Efficacy in Murine Models of SARS and COVID-19.
المؤلفون: Rappazzo CG; Adimab LLC, Lebanon, NH 03766, USA., Tse LV; Department of Epidemiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Kaku CI; Adimab LLC, Lebanon, NH 03766, USA., Wrapp D; Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA., Sakharkar M; Adimab LLC, Lebanon, NH 03766, USA., Huang D; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA., Deveau LM; Adimab LLC, Lebanon, NH 03766, USA., Yockachonis TJ; Paul G. Allen School of Global Animal Health, Washington State University, Pullman, WA 99164, USA., Herbert AS; U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA.; The Geneva Foundation, 917 Pacific Avenue, Tacoma, WA 98402, USA., Battles MB; Adimab LLC, Lebanon, NH 03766, USA., O'Brien CM; U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA.; The Geneva Foundation, 917 Pacific Avenue, Tacoma, WA 98402, USA., Brown ME; Adimab LLC, Lebanon, NH 03766, USA., Geoghegan JC; Adimab LLC, Lebanon, NH 03766, USA., Belk J; Adimab LLC, Lebanon, NH 03766, USA., Peng L; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA., Yang L; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA., Scobey TD; Department of Epidemiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Burton DR; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Cambridge, MA 02139, USA., Nemazee D; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA., Dye JM; U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA., Voss JE; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA., Gunn BM; Paul G. Allen School of Global Animal Health, Washington State University, Pullman, WA 99164, USA., McLellan JS; Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA., Baric RS; Department of Epidemiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.; Departments of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Gralinski LE; Department of Epidemiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Walker LM; Adimab LLC, Lebanon, NH 03766, USA.; Adagio Therapeutics, Inc., Waltham, MA 02451, USA.
المصدر: BioRxiv : the preprint server for biology [bioRxiv] 2020 Nov 17. Date of Electronic Publication: 2020 Nov 17.
نوع المنشور: Preprint
اللغة: English
بيانات الدورية: Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE
مستخلص: The recurrent zoonotic spillover of coronaviruses (CoVs) into the human population underscores the need for broadly active countermeasures. Here, we employed a directed evolution approach to engineer three SARS-CoV-2 antibodies for enhanced neutralization breadth and potency. One of the affinity-matured variants, ADG-2, displays strong binding activity to a large panel of sarbecovirus receptor binding domains (RBDs) and neutralizes representative epidemic sarbecoviruses with remarkable potency. Structural and biochemical studies demonstrate that ADG-2 employs a unique angle of approach to recognize a highly conserved epitope overlapping the receptor binding site. In murine models of SARS-CoV and SARS-CoV-2 infection, passive transfer of ADG-2 provided complete protection against respiratory burden, viral replication in the lungs, and lung pathology. Altogether, ADG-2 represents a promising broad-spectrum therapeutic candidate for the treatment and prevention of SARS-CoV-2 and future emerging SARS-like CoVs.
Competing Interests: Competing interests: C.G.R, C.I.K, M.S., L.M.D., M.B.B., M.E.B., J.C.G., and L.M.W. are employees of Adimab, LLC and may hold shares in Adimab, LLC. L.M.W. is an employee of Adagio Therapeutics Inc. and holds shares in Adagio Therapeutics Inc. D.R.B. is on the SAB of Adimab, LLC and Adagio Therapeutics Inc. and holds shares in Adimab, LLC.
معلومات مُعتمدة: R01 AI132317 United States AI NIAID NIH HHS; R01 AI073148 United States AI NIAID NIH HHS; R01 AI132178 United States AI NIAID NIH HHS; U19 AI142777 United States AI NIAID NIH HHS; P30 CA008748 United States CA NCI NIH HHS; U54 CA260543 United States CA NCI NIH HHS
تواريخ الأحداث: Date Created: 20201125 Latest Revision: 20231019
رمز التحديث: 20240829
مُعرف محوري في PubMed: PMC7685319
DOI: 10.1101/2020.11.17.385500
PMID: 33236009
قاعدة البيانات: MEDLINE
الوصف
DOI:10.1101/2020.11.17.385500