Jana Jacobs, PhD, has been awarded funding $50,000 for a one-year grant by the University of Pittsburgh Clinical and Translational Science Institute (CTSI) which is an integral part of the National Institutes of Health (NIH) nationwide network. Jana’s grant entitled “SARS-CoV-2 Immune Escape Variants in Treatment,” was one of 17 funded submissions from a pool of 157 applications.
Current SARS-CoV-2/COVID-19 research is a rapidly changing landscape of treatment and prevention strategies, many of which rely on virus neutralization by antibodies. The speed of innovation has out-paced the study of viral evolution; many treatment and prevention strategies are moving forward before there has been ample analysis for escape variants. As the virus continues to spread, it is prudent to expect emergence of immune escape variants. This project will apply cutting-edge methods of sequence analysis, mutagenesis of the S gene, pseudovirus production, and neutralization assays to assess immune selection and viral escape.
Currently identified variants will be tested and the emergence of new variants and their impact on antibody sensitivity will be monitored. Variants that show resistance to current monoclonal antibodies (mAbs) or convalescent serum will trigger the search for more broadly neutralizing mAbs with collaborators at the Infectious Diseases’ Center for Antibody Therapeutics (CAT).
This study will help define the importance of viral variants and provide the knowledge necessary to refine antibody-based therapeutics that confer broad neutralization against circulating SARSCoV-2 variants. This pilot will also lead to more in-depth studies of the structural and mechanistic basis of immune escape and to novel immunogen and antibody designs to prevent immune escape of SARS-CoV-2 and other pathogenic coronaviruses.