ZRC3308 Monoclonal Antibody Cocktail Shows Protective Efficacy in Syrian Hamsters against SARS-CoV-2 Infection

Abstract

We have developed a monoclonal antibody (mAb) cocktail (ZRC-3308) comprising of ZRC3308-A7 and ZRC3308-B10 in the ratio 1:1 for COVID-19 treatment. The mAbs were designed to have reduced immune effector functions and increased circulation half-life. mAbs showed good binding affinities to non-competing epitopes on RBD of SARS-CoV-2 spike protein and were found neutralizing SARS-CoV-2 variants B.1, B.1.1.7, B.1.351, B.1.617.2, and B.1.617.2 AY.1 in vitro. The mAb cocktail demonstrated effective prophylactic and therapeutic activity against SARS-CoV-2 infection in Syrian hamsters. The antibody cocktail appears to be a promising candidate for prophylactic use and for therapy in early COVID-19 cases that have not progressed to severe disease.

Compellingly high SARS-CoV-2 susceptibility of Golden Syrian hamsters suggests multiple zoonotic infections of pet hamsters during the COVID-19 pandemic

“…Therefore, this route was used for all subsequent studies. Since the intranasal route was used in almost all other published studies (Chiba et al, 2022;Meseda et al, 2021;Taylor et al, 2021;Yadav et al), and to the best of our knowledge no report of an orotracheal SARS-CoV-2 inoculation of hamsters has been published so far, a direct comparison between previously published experiments and our study is not feasible.…”

“…Today, Golden Syrian hamsters are the leading animal model in SARS-CoV-2 research, in particular for vaccine and drug efficacy studies (Chiba et al, 2022;Meseda et al, 2021;Taylor et al, 2021;Yadav et al), since they mirror the moderate disease phenotype of human patients with a complete recovery within 14 days (Gruber, Firsching, Trimpert, & Dietert, 2021). When establishing this model, we initially used an infection dose of 1*10 5 TCID50, and found the orotracheal infection route to induce a more prominent weight loss and viral shedding, the latter exceeding those obtained after intranasal infection by at least a factor of 5.…”

Compellingly high SARS-CoV-2 susceptibility of Golden Syrian hamsters suggests multiple zoonotic infections of pet hamsters during the COVID-19 pandemic

“…Therefore, this route was used for all subsequent studies. Since the intranasal route was used in almost all other published studies 27 , 28 , 30 , and to the best of our knowledge no report of an orotracheal SARS-CoV-2 inoculation of hamsters has been published so far, a direct comparison between previously published experiments and our study is not feasible.…”

“…Today, Golden Syrian hamsters are the leading animal model in SARS-CoV-2 research, in particular for vaccine and drug efficacy studies 27 – 30 , since they mirror the moderate disease phenotype of human patients with a complete recovery within 14 days 31 . When establishing this model, we initially used an infection dose of 1 * 10 5 TCID 50 , and found the orotracheal infection route to induce a more prominent weight loss and viral shedding, the latter exceeding those obtained after intranasal infection by at least a factor of 5.…”

Therapeutic antibodies for COVID-19: is a new age of IgM, IgA and bispecific antibodies coming?

“… Human IgG B cells of convalescent pts RBD - - 79 MW06 Human IgG1 B cells of a convalescent pt RBD Cross-reactivity against SARS-CoV-1 and SARS-CoV-2; form a cocktail with MW05 against SARS-CoV-2 - 80 1H1, etc. Rabbit IgG Immunized rabbit RBD - - 81 ZRC3308-A7 ZRC3308-B10 Humanized IgG1 - RBD Form a cocktail named ZRC-3308 - 82 IMM-BCP-01 - - S A cocktail consisting of three antibodies with non-overlapping bindings - - Cytokine and chemokine Tocilizumab a Humanized IgG1κ Mouse IL-6 R EUA in USA Phase 2/3/4 (NCT04317092, etc.) 83 Levilimab Human IgG1 - IL-6 R Approved in Russia Phase 3 (NCT04397562) 84 Olokizumab Humanized IgG4κ ...…”