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.
Highlights
ZRC3308-A7 precaptured channels and vice versa, indicating that both the antibodies bind to distinct epitopes on receptor-binding domain (RBD) of spike protein as depicted in sensograms in terms of response units (RU) vs time (Figure 1g,h)
Vaccines against SARS-CoV-2 have been rolled out as prophylactic interventions, but the treatment options are still very limited. monoclonal antibody (mAb) appear to be promising candidates for SARS-CoV-2, as is evident by the Emergency Use Authorization (EUA) received by 3 mAb therapies from USFDA, which have been granted approvals in other countries [15,16,17]
The ZRC3308 mAbs showed good binding affinity, similar to other mAb products for treatment for SARSCoV-2 [16]. As these antibodies bind non-competitively to the RBD of the spike protein and are equipotent in terms of binding to RBD and virus neutralization potential, the 1:1 cocktail diminishes the ability of variants to escape the treatment
Summary
Since the first report of occurrence of SARS-COV-2 infection in China on 30 December. 2019, the virus has spread rapidly worldwide, accounting for more than 200 million cases and 4 million deaths as of 9 August 2021 [1]. Even though more than twenty vaccines have been granted Emergency Use Authorization (EUA) in multiple countries, the vaccination rate is skewed globally due to the limited accessibility to low- and middle-income countries [2,3]. Due to the inequitable access of vaccines and emergence of new variants with immune escape property, the development of herd immunity may take years [3]. Convalescent plasma transfusion has been used as a therapeutic option in the case of novel viral diseases such as Ebola virus disease, SARS, MERS, and coronavirus disease
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