Preclinical Efficacy of IMM-BCP-01, a Highly Active Patient-Derived Anti-SARS-CoV-2 Antibody Cocktail

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 a...

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Bibliographic Details
Published in:bioRxiv 2022-05
Main Authors: Nikitin, Pavel A, Dimuzio, Jillian M, Dowling, John P, Patel, Nirja B, Bingaman-Steele, Jamie L, Nicolescu, Chris, Heimbach, Baron C, Henriquez, Noeleya, Sikorsky, Eden L, Polley, Antonio, Howanski, Raymond J, Nath, Mitchell, Shukla, Halley, Scheaffer, Suzanne M, Finn, James P, Li-Fang, Liang, Smith, Todd, Storm, Nadia, Mckay, Lindsay Ga, Johnson, Rebecca I, Malsick, Lauren E, Honko, Anna N, Griffiths, Anthony, Diamond, Michael S, Sarma, Purnanand, Geising, Dennis H, Morin, Michael J, Robinson, Matthew K
Format: Article
Language:English
Subjects:
ACE2
Angiotensin-converting enzyme 2
Antibodies
Antiviral activity
Biotechnology
Complement activation
COVID-19
Epitopes
Immunological memory
Monomers
Patent applications
Patients
Phagocytosis
Severe acute respiratory syndrome coronavirus 2
Spike protein
Trimers
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Summary: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. Competing Interest Statement The described approach, antibodies and cocktail composition have been included in patent applications. PAN, JMD, JPD, NBP, JLBS, BCH, NH, CN, AP, MN, HS, JPF, LFL, TS, PS, DHG, MJM and MKR are employees and shareholders of Immunome, Inc. MSD is a consultant for Inbios, Vir Biotechnology, and Carnival Corporation, and on the Scientific Advisory Boards of Moderna and Immunome. MSD has stock equity options from Immunome. The Diamond laboratory has received funding support in sponsored research agreements from Immunome, and unrelated support from Vir Biotechnology, Moderna, and Emergent BioSolutions.
DOI:10.1101/2021.10.18.464900