Identification of Serodiagnostic Epitopes for SARS-CoV-2, Endemic Human Coronaviruses and Influenza Virus A novel human coronavirus, which causes severe acute respiratory disease, now known as SARS- CoV-2 emerged in December 2019. Infection with SARS-CoV-2 spread rapidly worldwide and on 11 March 2020 it was declared a pandemic by the World Health Organization. As of 4 September 2020, there are over 26 million confirmed cases of coronavirus infectious disease (COVID-19) caused by this new virus, resulting in more than 870,000 deaths, corresponding to a mortality rate of ~3.3%, although the mortality rate varies widely from country to country and is subject to considerable uncertainty. Best current estimates indicate that SARS-CoV-2 has a basic reproductive number, R0, of 2 to 2.5 and an incubation time of approximately 4.6 days, which allow rapid spread of SARS-CoV-2. The USA has more cases of COVID-19 and more deaths from the disease than any other country. Since the beginning of this pandemic the scientific community came together in an unparalleled effort to advance diagnostic and vaccine development and despite all this effort and some of the success is it has brought we are still nowhere near the end of this pandemic. Although laboratory tests for the SARS-CoV-2 genome and antibodies have been developed, a reliable point-of care (POC) test for antibodies to SARS-CoV-2 and influenza virus that does not cross-react with endemic human coronaviruses (HCoVs) is still urgently needed to guide clinical care as well as public health measures including opening schools, businesses and public gatherings. Given the impending influenza season it will be critical to have fast and specific test to distinguish between those three causes of respiratory infection with partially overlapping symptoms. We therefore seek an R43 grant to create a large protein and peptide microarray for identification of the best antigens and epitopes for sensitive and specific detection of serum antibodies reactive with SARS-CoV-2 and influenza virus. Next, we will create a sensitive and specific ELISA for antibodies to SARS-CoV-2 and will collaborate with others to create a rapid antibody assay suitable for use at the point of care. This will greatly facilitate public health and medical responses to the ongoing outbreak of COVID-19, seasonal influenza and for future waves of disease which may occur. We propose a novel approach to discovery of the best antigens or epitopes for sensitive and specific detection of infection by SARS-CoV-2 and influenza virus and for distinguishing antibodies to SARS-CoV-2 from antibodies to endemic HCoVs. Our specific aims are: 1) add the major structural proteins of currently circulating influenza viruses, HCoV-229E and HCoV- HKU1, as well as peptides and fragments of these proteins to our existing coronavirus protein microarray, (2) develop and validate a diagnostic algorithm for distinguishing SARS-CoV-2 from infection by the four endemic HCoVs and for detecting new influenza virus infection and (3) create and test prototype antibody ELISAs for sensitive and specific detection of antibodies to SARS-CoV-2. Public Health Relevance Statement Narrative - Identification of Serodiagnostic Epitopes for SARS-CoV-2, Endemic Human Coronaviruses and Influenza Virus A novel human coronavirus, which causes severe acute respiratory disease, now known as SARS-CoV-2 emerged in December 2019, spread rapidly worldwide and is now a pandemic with over 26 million confirmed cases resulting in over 870,000 deaths. A sensitive and specific point of care test for antibodies to SARS-CoV- 2 is needed to guide clinical care as well as public health measures including opening schools, businesses and public gatherings, but current point of care serological tests for antibodies to SARS-CoV-2 are not sufficiently reliable. We will therefore create a comprehensive protein and peptide microarray for identification of the best serodiagnostic antigens and epitopes and will develop a sensitive and specific test for SARS-CoV-2 antibodies; we will also begin doing the same for influenza virus.
Project Terms: No Project Terms available.
