Discovery of SARS-CoV-2 neutralizing Abs for therapy, prophylaxis and vaccine development.

NIH RePORTER · NIH · UM1 · $188,714 · view on reporter.nih.gov ↗

Abstract

This application is being submitted in response to NOT-AI-20-030 Coronaviruses (CoVs) are enveloped, positive-sense, single-stranded RNA viruses and the subfamily consists of only 2 members, Alpha- and Betacoronavirus which infect mammals and generally result in respiratory illnesses. In 2019, the World Health Organization was notified of a cluster of pneumonia cases possibly originating from a seafood market in Wuhan city, Hubei Province, China. Within three weeks, a total of 198 cases of novel coronavirus-infected pneumonia were confirmed, and an analysis of 138 cases at the Zhongnan Hospital of Wuhan University found a mortality rate of 4.3%. As of February 25, 2020, there were 79,331 confirmed cases of a clinical syndrome now called COVID-19, as the result of infection by a novel virus named SARS-CoV-2. The rapid global spread of COVID-19 is possible in part because there is no clinically approved treatment or vaccine for SARS-CoV-2. This supplement application will leverage our existing expertise in antibody discovery and characterization to rapidly identify pan-CoV neutralizing antibodies. Recovered Abs will function both as lead therapeutics to address the ongoing COVID-19 outbreak and tools for evaluating candidate vaccines, by addressing 3 Specific Aims: Aim 1: Isolation of SARS-CoV-2 neutralizing antibodies. Antibodies will be isolated from plasmablasts (acute infection) and memory B cells (convalescence) of COVID-19 patients. Aim 2: Characterization of pan-CoV neutralizing antibodies. Isolated mAbs will be screened for neutralization using a SARS-CoV-2 pseudovirus assay as well as a panel of Betacoronavirus pseudoviruses to determine the breadth of neutralization across the Coronavirus subfamily. Aim 3: Optimization of potency and developability of neutralizing antibodies. Antibodies in the most promising cocktail will be affinity matured to improve their overall potency and to remove potential manufacturing liabilities.

Key facts

NIH application ID
10130218
Project number
3UM1AI144462-01S2
Recipient
SCRIPPS RESEARCH INSTITUTE, THE
Principal Investigator
Dennis R. Burton
Activity code
UM1
Funding institute
NIH
Fiscal year
2020
Award amount
$188,714
Award type
3
Project period
2020-05-01 → 2026-06-30