Rapid discovery and characterization of monoclonal antibodies against the SARS-CoV-2 Delta spike protein

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In the fall of 2021, the Delta variant of SARS-CoV-2 was the dominant strain in the US, being both more contagious than previous variants and more likely to lead to “long COVID” than subsequent Omicron variants. Here we describe the discovery and characterization of a large number of Delta spike-binding monoclonal antibodies (mAbs). By combining detailed DNA sequence analysis and binding assays, we identified 96 candidates for further analysis and development. Many of these hits exhibited neutralizing activity and also cross-reacted with one or more of the wild-type virus, Omicron 1.1.529, BA.2 and BA.5 variants.

The COVID-19 pandemic has led to a rapid and wide-ranging search for therapeutics to protect against and treat the illness. Besides the vaccines and antivirals that have been developed against SARS-CoV-2, a number of mAbs have been given emergency use authorization (EUA) by the FDA. Unfortunately, the neutralizing effect of mAb therapeutics can be reduced or negated by the evolution of viral variants. For this reason, the expedited discovery and development of new mAbs with neutralizing activity selective for novel variants is essential.

These techniques can also be used to rapidly discover antibodies for the treatment of cancers, neurodegenerative diseases (e.g., Alzheimer’s) and emerging infectious diseases.

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