Development of SARS-CoV-2 specific neutralizing recombinant monoclonal antibodies

Abstract

Development of effective therapeutic strategies to combat COVID-19 relies on understanding the cellular and molecular mechanisms of infection. Antibodies specific to SARS-CoV-2 aid in accelerating research to characterize viral protein function and immune response to infection. An urgent need for SARS-CoV-2 specific antibodies arose, as several antibodies already available in the market cross-reacted with other members of the coronavirus family. To address this need for specificity and urgency, we collaborated with a leading pharmaceutical company to develop antibodies specific to SARS-CoV-2. We generated a single chain fragment variable (scFv) library for SARS-CoV-2 using computational expansion of published antibody structures against SARS-CoV-1. This enabled us to make recombinant antibodies in record time of 3 months. These synthetic sequences were grafted onto both human and human-rabbit chimeric Fc enabling use of these antibodies in a multitude of immunoassays. Our antibodies were targeted against the SARS-CoV-2 spike protein; the receptor binding domain in the spike protein plays a vital role in viral entry into host cells and subsequent infection, making it an important target for neutralizing antibodies and antiviral treatments. Some of our antibodies demonstrate neutralizing capabilities, making them a valuable tool to study neutralizing antibody response to infection. These antibodies are specific to SARS-CoV-2 and do not cross-react with other coronaviruses. The specificity and versatility of our antibodies enables scientists to better understand SARS-CoV-2 and potentially aid in developing therapeutic strategies against COVID-19 which continues to be important as newer variants of the virus emerge.