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Preclinical Efficacy of IMM-BCP-01, a Highly Active Patient-Derived Anti-SARS-CoV-2 Antibody Cocktail
Pavel A Nikitin; Jillian M DiMuzio; John P Dowling; Nirja B Patel; Jamie L Bingaman-Steele; Chris Nicolescu; Baron C Heimbach; Noeleya Henriquez; Eden L Sikorsky; Antonio Polley; Raymond J Howanski; Mitchell Nath; Halley Shukla; Suzanne M. Scheaffer; James P Finn; Li-fang Liang; Todd Smith; Nadia Storm; Lindsay G.A. McKay; Rebecca I Johnson; Lauren E Malsick; Anna N Honko; Anthony Griffiths; Michael S Diamond; Purnanand Sarma; Dennis H Geising; Michael J Morin; Matthew K Robinson.
Affiliation
  • Pavel A Nikitin; Immunome, Inc
  • Jillian M DiMuzio; Immunome, Inc
  • John P Dowling; Immunome, Inc
  • Nirja B Patel; Immunome, Inc
  • Jamie L Bingaman-Steele; Immunome, Inc
  • Chris Nicolescu; Immunome, Inc
  • Baron C Heimbach; Immunome, Inc
  • Noeleya Henriquez; Immunome, Inc
  • Eden L Sikorsky; Immunome, Inc
  • Antonio Polley; Immunome, Inc
  • Raymond J Howanski; Immunome, Inc
  • Mitchell Nath; Immunome, Inc
  • Halley Shukla; Immunome, Inc
  • Suzanne M. Scheaffer; Departments of Medicine, Molecular Microbiology, Pathology & Immunology, Washington University School of Medicine
  • James P Finn; Immunome, Inc
  • Li-fang Liang; Immunome, Inc
  • Todd Smith; Immunome, Inc
  • Nadia Storm; Boston University School of Medicine and National Emerging Infectious Diseases Laboratories
  • Lindsay G.A. McKay; Boston University School of Medicine and National Emerging Infectious Diseases Laboratories
  • Rebecca I Johnson; Boston University School of Medicine and National Emerging Infectious Diseases Laboratories
  • Lauren E Malsick; Boston University School of Medicine and National Emerging Infectious Diseases Laboratories
  • Anna N Honko; Boston University School of Medicine and National Emerging Infectious Diseases Laboratories
  • Anthony Griffiths; Boston University School of Medicine and National Emerging Infectious Diseases Laboratories
  • Michael S Diamond; Departments of Medicine, Molecular Microbiology, Pathology & Immunology, Washington University School of Medicine
  • Purnanand Sarma; Immunome, Inc
  • Dennis H Geising; Immunome, Inc
  • Michael J Morin; Immunome, Inc
  • Matthew K Robinson; Immunome, Inc
Preprint in English | bioRxiv | ID: ppbiorxiv-464900
ABSTRACT
Using an unbiased interrogation of the memory B cell repertoire of convalescent COVID-19 patients, we identified human antibodies that demonstrated robust antiviral activity in vitro and efficacy in vivo against all tested SARS-CoV-2 variants. Here, we describe the pre-clinical characterization of an antibody cocktail, IMM-BCP-01, that consists of three unique, patient-derived recombinant neutralizing antibodies directed at non-overlapping surfaces on the SARS-CoV-2 spike protein. Two antibodies, IMM20184 and IMM20190 directly block spike binding to the ACE2 receptor. Binding of the third antibody, IMM20253, to its unique epitope on the outer surface of RBD, alters the conformation of the spike trimer, promoting release of spike monomers. These antibodies decreased SARS-CoV-2 infection in the lungs of Syrian golden hamsters, and efficacy in vivo efficacy was associated with broad antiviral neutralizing activity against multiple SARS-CoV-2 variants and robust antiviral effector function response, including phagocytosis, ADCC, and complement pathway activation. Our pre-clinical data demonstrate that the three antibody cocktail IMM-BCP-01 shows promising potential for preventing or treating SARS-CoV-2 infection in susceptible individuals. One sentence summaryIMM-BCP-01 cocktail triggers Spike Trimer dissociation, neutralizes all tested variants in vitro, activates a robust effector response and dose-dependently inhibits virus in vivo.
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Full text: Available Collection: Preprints Database: bioRxiv Type of study: Prognostic study Language: English Year: 2021 Document type: Preprint
Full text: Available Collection: Preprints Database: bioRxiv Type of study: Prognostic study Language: English Year: 2021 Document type: Preprint
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