STTR Phase I: A platform for the rapid discovery of human antibodies as therapeutics for infectious disease (COVID-19)

The broader impacts of this Small Business Technology Transfer (STTR) Phase I project are to establish a novel and rapid drug-discovery platform aimed at infectious diseases. An opportunity is to tap into an unexplored diversity of human antibodies and develop them into therapies. This technology aims to identify drug candidates and select therapeutic candidates quickly. The established platform will be poised to counter emerging outbreaks and existing stubborn pathogen such as drug-resistant bacteria. The priority is the current COVID-19 pandemic, but this can be expanded to other potential pathogens. This STTR Phase I project will establish a novel discovery platform of human antibody therapeutics to counter infectious diseases. The rise of devastating new pathogens, such as SARS-CoV-2 (COVID-19) and antibiotic-resistant bacteria, calls for alternative and rapid therapeutic approaches. Traditional therapeutic antibody development generally involves animal models or/and affinity selection systems. They are expensive and lengthy, requiring multiple steps, including humanization, to mitigate immune neutralization. The proposed method identifies human antibodies (IgG) targeting a pathogen of interest in only nine days. The approach also capitalizes on an unexplored diversity of human antibodies. The pipeline begins with a collection of donor cells containing plasmablasts, which are modified to capture own-secreted IgG allowing for the enrichment of the relevant cells. The cells are sorted in single wells in a high throughput fashion. The process continues with high throughput cloning, antibody expression, and a preliminary binding and neutralization screen. The pipeline lasts nine days from cells to the initial binding screen, identifying hundreds of antibodies of varying characteristics. The initial screen is followed by further tests of binding kinetics and neutralization assays. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.