Projects
UNDERSTANDING IMMUNE RESPONSES TO CORONAVIRUS INFECTION AND VACCINATION
Topic: Coronaviruses
Summary
Non Technical Summary
Although coronaviruses affect many different species of mammals and birds around the world, the immune response to vaccination or infection remains poorly understood. The overarching goals of this project are to understand immune responses to coronavirus vaccination, improve vaccine strategies for these viruses, and identify ways to predict animals that are and are not at risk for developing severe disease. Vaccines in current use for coronaviruses rarely produce lasting protection from infection and, at best, are only able protect from severe disease. Even the ability to predict an animal at low risk of severe disease after vaccination is challenging. By better understanding what component of the immune system elicits protection from severe disease, better vaccines, tests, and management strategies can be developed to minimize the impact of infection on livestock, companion animals, humans.
Objectives & Deliverables
Goals / Objectives
This project is designed to better understand protective and nonprotective immune responses to coronavirus infections and vaccines. Coronaviruses affect a vast array of veterinary species including both mammals and birds. While the immune response to infection has been well-characterized for many of the human coronaviruses, these data are lacking among responses to coronaviruses of veterinary importance. We will characterize responses to viruses in the Alphacoronavirus genus, with emphasis on determining important lymphocyte subsets as well as antigen specificity. This knowledge will help to predict protection from disease as well as to guide optimal prophylaxis strategies.This project is designed to better understand protective and nonprotective immune responses to coronavirus infections and vaccines. Coronaviruses affect a vast array of veterinary species including both mammals and birds. While the immune response to infection has been well-characterized for many of the human coronaviruses, these data are lacking among responses to coronaviruses of veterinary importance. We will characterize responses to viruses in the Alphacoronavirus genus, with emphasis on determining important lymphocyte subsets as well as antigen specificity. This knowledge will help to predict protection from disease as well as to guide optimal prophylaxis strategies.
Challenges
Project Methods
In this project, we will vaccinate animals against coronavirus using a novel platform (mRNA vaccine) and a coronavirus antigen not commonly used (nucleocapsid), as previous data indicate that cytotoxic T cell responses to this protein are protective against severe disease. We will then collect biological samples from these animals to assay immune responses to the vaccine. Samples will include isolated peripheral blood mononuclear cells and serum. Mononuclear cells will be assayed by flow cytometry and intracellular cytokine staining after peptide pool activation to determine which cell types/subsets are most responsive to nucleocapsid, with the potential to switch to ELISpot plates if needed due to lack of flow cytometry reagents for some veterinary species. Serum collected from vaccinated animals will be assayed by ELISA for specific antibody titers to nucleocapsid as well. Statistical analysis will be performed to compare vaccinated from unvaccinated animals.
