1), two separate mouse strains were immunized with the S1 subunit (which contains the receptor binding domain): a humanized strain to facilitate the discovery of fully human antibodies (Alloy-GK mice), and an engineered mouse strain designed to elicit greater epitopic diversity and overall immune response (Abveris DiversimAb™ mice). This report highlights several different techniques and antibody discovery workflows leveraged in the discovery and characterization of antibody panels targeting the spike protein (S) of SARS-CoV-2 and showcases screening results for a subset of representative candidates. The present study focuses on optimizing the in vivo discovery timeline by introducing compressed workflows for immunization, primary cell screening and antibody characterization while maintaining or improving screening depth to elucidate desired properties faster. For example, traditional in vitro naïve library panning or in vivo hybridoma generation can take 6 months or longer to move from target ID to lead candidate selection. The ability to rapidly perform the discovery tasks within this scope requires novel technologies, strategies and efficiencies to maintain the required throughput and depth of screening. Both have served the industry well for decades however, in recent years the traditionally lengthy timeline required to move from target identification through lead candidate discovery has been challenged. When taken in aggregate, these criteria are quite stringent and therefore necessitate efficient, high-resolution screening strategies to identify valuable lead candidates.ĭevelopment of viable therapeutic antibody candidates typically follows one of two principal methodologies: in vitro or in vivo discovery. These antibodies, which can function either alone or in combination with oligoclonal mixtures of non-competing antibodies, harbor basic properties like receptor blocking activity and high affinity. In general, the most valuable and broadly applicable antiviral antibodies are those that exhibit cross-reactivity to related viruses and are unaffected by escape mutant evolutionary pressures. In particular, the understanding that neutralizing antibody function is fundamental to combating disease progression helped streamline early antibody-based drug therapy discovery strategies.īeyond direct therapeutic use, antibodies can help inform vaccine design to enable next-generation vaccine development with a focus on relevant viral epitopes. Lessons learned from these public health threats helped guide the strategy for the accelerated response to COVID-19. The response to the COVID-19 pandemic mirrored that of other recent viral outbreaks, including, but not limited to, H1N1 influenza in 2009, Ebola Virus in 2014 and Zika Virus in 2015. Within weeks of the emergence of viral pneumonia outbreaks in Wuhan, China, deep sequencing had identified the cause, and the resulting mobilization of widespread therapeutic and prophylactic discovery efforts ensued. The pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), or coronavirus disease 2019 (COVID-19), has received unprecedented attention from the scientific community in an effort to rapidly develop efficacious treatments and vaccines.
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