PI: Anita McElroy
Co-PIs: Paul Duprex and Alan Wells
Title: SARS-CoV-2 clinical and community serosurveillance
Description: COVID19 no longer requires an introduction since the entire globe is dealing with a worldwide pandemic due to SARSCoV2. Most individuals infected with SARSCoV2 will have mild self-limiting symptoms, and some may even be asymptomatic. This has made control of virus spread quite difficult and has necessitated the drastic measures of social distancing and governmental orders of shelter in place. With testing currently restricted to acute cases and even that being limited due to resource shortages, it is impossible to know how widespread the disease is within the community or within the hospital setting. These data are desperately needed to augment public health efforts to control the spread of the virus and furthermore would hasten our return to normal societal behaviors. In this proposal we seek to develop serologic assays that can quantitate human humoral immune responses to SARSCoV2. These data will inform on how widespread the disease is in the community since these assays will be able to identify individuals who were previously infected but whose symptoms were not severe enough to necessitate hospitalization, or acute phase testing. Importantly, these assays have the potential to speed up our return to normalcy since individuals who have seroconverted would be expected to be immune to re-infection or at least protected from severe disease, and therefore safe to return to work and school settings that would put them in contact with others.
The clinical Immunopathology laboratory has developed a test that can detect IgG and IgA antibodies, and other tests are available that detect IgM/IgG against the virus. However, as these are positive in hospitalized patients with severe disease, they are of limited value in determining immunity, and thus identifying patients able to return to work, and define the necessary ‘herd immunity’.
The following scope of work is being proposed:
- Define an enzyme linked immunosorbent assay (ELISA) to detect neutralizing antibodies against SARSCoV2. We need a test that identifies neutralizing antibodies. Several different antigenic targets will be assessed- three different forms of the viral surface protein (known as the spike) as well as the viral nucleoprotein which is the most abundantly produced protein and likely to be the most immunogenic target of the immune system. Purified proteins and whole cell lysates will be assessed in these assays. Positive and negative control serum will be derived from known clinical cases (provided by Dr. Wells). This is a traditional approach that will use an indirect detection method. These types of assays are commonly performed in clinical labs around the world and would be easily translatable into any clinical setting.
- Develop and validate a microneutralization assay to determine whether these antibodies are neutralizing antibodies against the SARSCoV2 virus. The development of neutralizing antibodies is a classic correlate of immune mediated protection from infection. Using live SARSCoV2 in the Regional Biocontainment lab BSL-3, we will develop an assay that can quantitate the neutralizing antibodies that are present in the serum of patients and controls. This assay will also have utility in the convalescent serum passive immunization and future vaccine trials, as these trials will seek to establish a correlate of vaccine mediated protection and it will be critical to compare vaccine mediated immunity with naturally acquired immunity.
- Define the kinetics of the serological response from acute infection into convalescence in patients with COVD19. Serial samples (provided by Dr. Wells) will be tested in the SARSCoV2 ELISA and microneutralization assays to determine when in the course of disease SARSCoV2 specific antibody responses can be detected and will quantitate the magnitude of these responses.
- Define the level of community seroconversion. Using SARSCoV2 ELISA assays and microneutralization assays we will screen normal healthy community members for evidence of prior disease. These individuals will be recruited under a normal healthy phlebotomy protocol that is currently undergoing IRB review.
Source: Clinical and Translational Science Institute
Term: 1 year