Rapid Discovery And Characterization Of Monoclonal Antibodies Against The SARS-CoV-2 Delta Spike Protein

By Margaret Wong Ho, General Manager and Site Head; Christine L. Hsieh, Senior Scientist II, Cellular Immunology Assay Development; Xiaomei Ge, Senior Scientist II; Dan Luo, Senior Scientist II; and Brian A. Zabel, Senior Director, Curia Global, Inc.

Leveraging our advanced PentaMice® wild-type mice for optimal immunizations, along with single B cell selection using Opto® Plasma B Discovery 4.0 workflows on the Berkeley Lights® Beacon® Optofluidic System, and rapid sequencing coupled with developability analysis, Curia's First-to-Human antibody discovery service boasts an accelerated path from hits to leads in just 120–240 days.

Amid the fall of 2021, the Delta variant of SARS-CoV-2 emerged as the dominant strain in the US, characterized by heightened contagiousness and a higher likelihood of causing "long COVID" compared to subsequent Omicron variants. Our discovery and characterization efforts resulted in the identification of numerous Delta spike-binding monoclonal antibodies (mAbs), with 96 candidates exhibiting promising neutralizing activity and cross-reactivity against wild-type virus, Omicron variants, and more.

The urgency of the COVID-19 pandemic has prompted an extensive quest for therapeutics, including vaccines, antivirals, and mAbs authorized for emergency use by the FDA. However, the evolving nature of viral variants underscores the critical need for expedited discovery and development of mAbs with selective neutralizing activity against novel variants. These innovative techniques not only facilitate swift responses to emerging infectious diseases like COVID-19 but also hold promise for rapidly discovering antibodies to combat cancers and neurodegenerative diseases such as Alzheimer's.

In this comprehensive white paper, the authors delve into the intricate workflow employed for the discovery and characterization of monoclonal antibodies (mAbs) targeting the Delta spike protein.