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

Monoclonal antibodies are an efficacious therapy against 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 convalescent COVID-19 patients, 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, 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 non-overlapping 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 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 pre-clinical 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.