IMM-BCP-01, a patient-derived anti-SARS-CoV-2 antibody cocktail, is active across variants of concern including Omicron BA.1 and BA.2.

Autor: Nikitin PA; Immunome Inc., Exton, PA 19341, USA., DiMuzio JM; Immunome Inc., Exton, PA 19341, USA., Dowling JP; Immunome Inc., Exton, PA 19341, USA., Patel NB; Immunome Inc., Exton, PA 19341, USA., Bingaman-Steele JL; Immunome Inc., Exton, PA 19341, USA., Heimbach BC; Immunome Inc., Exton, PA 19341, USA., Henriquez N; Immunome Inc., Exton, PA 19341, USA., Nicolescu C; Immunome Inc., Exton, PA 19341, USA., Polley A; Immunome Inc., Exton, PA 19341, USA., Sikorski EL; Immunome Inc., Exton, PA 19341, USA., Howanski RJ; Immunome Inc., Exton, PA 19341, USA., Nath M; Immunome Inc., Exton, PA 19341, USA., Shukla H; Immunome Inc., Exton, PA 19341, USA., Scheaffer SM; Departments of Medicine, Molecular Microbiology, Pathology, and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA., Finn JP; Immunome Inc., Exton, PA 19341, USA., Liang LF; Immunome Inc., Exton, PA 19341, USA., Smith T; Immunome Inc., Exton, PA 19341, USA., Storm N; Department of Microbiology, Boston University School of Medicine and National Emerging Infectious Diseases Laboratories, Boston, MA, USA., McKay LGA; Department of Microbiology, Boston University School of Medicine and National Emerging Infectious Diseases Laboratories, Boston, MA, USA., Johnson RI; Department of Microbiology, Boston University School of Medicine and National Emerging Infectious Diseases Laboratories, Boston, MA, USA., Malsick LE; Department of Microbiology, Boston University School of Medicine and National Emerging Infectious Diseases Laboratories, Boston, MA, USA., Honko AN; Department of Microbiology, Boston University School of Medicine and National Emerging Infectious Diseases Laboratories, Boston, MA, USA., Griffiths A; Department of Microbiology, Boston University School of Medicine and National Emerging Infectious Diseases Laboratories, Boston, MA, USA., Diamond MS; Departments of Medicine, Molecular Microbiology, Pathology, and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA., Sarma P; Immunome Inc., Exton, PA 19341, USA., Geising DH; Immunome Inc., Exton, PA 19341, USA., Morin MJ; Immunome Inc., Exton, PA 19341, USA., Robinson MK; Immunome Inc., Exton, PA 19341, USA.
Jazyk: angličtina
Zdroj: Science immunology [Sci Immunol] 2022 Sep 09; Vol. 7 (75), pp. eabl9943. Date of Electronic Publication: 2022 Sep 09.
DOI: 10.1126/sciimmunol.abl9943
Abstrakt: Monoclonal antibodies are an efficacious therapy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, rapid viral mutagenesis led to escape from most of these therapies, outlining the need for an antibody cocktail with a broad neutralizing potency. Using an unbiased interrogation of the memory B cell repertoire of patients with convalescent COVID-19, we identified human antibodies with broad antiviral activity in vitro and efficacy in vivo against all tested SARS-CoV-2 variants of concern, including Delta and Omicron BA.1 and BA.2. Here, we describe an antibody cocktail, IMM-BCP-01, that consists of three patient-derived broadly neutralizing antibodies directed at nonoverlapping surfaces on the SARS-CoV-2 Spike protein. Two antibodies, IMM20184 and IMM20190, directly blocked Spike binding to the ACE2 receptor. Binding of the third antibody, IMM20253, to its cryptic epitope on the outer surface of RBD altered the conformation of the Spike Trimer, promoting the release of Spike monomers. These antibodies decreased Omicron SARS-CoV-2 infection in the lungs of Syrian golden hamsters in vivo and potently induced antiviral effector response in vitro, including phagocytosis, ADCC, and complement pathway activation. Our preclinical data demonstrated that the three-antibody cocktail IMM-BCP-01 could be a promising means for preventing or treating infection of SARS-CoV-2 variants of concern, including Omicron BA.1 and BA.2, in susceptible individuals.
Databáze: MEDLINE
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