Role of Salivary Gland Localized SARS-CoV-2 Infection in Oral Tolerance & Immunization Efficacy

Project Summary | Role of Salivary Gland Localized SARS-CoV-2 Infection in Oral Tolerance & Immunization Efficacy Over 5 million individuals in the United States have been diagnosed with systemic acute respiratory syndrome coronavirus-2, SARS-CoV-2, infections 1. One of the primary unanswered questions is whether patients that recover from SARS-CoV-2 or are immunized against SARS-CoV-2 will develop lasting immunity. Early reports of COVID-19 have outlined the potential role of salivary gland (SG) localized SARS-CoV-2 in the development of COVID-19 symptomology. Viruses that are able to infect the salivary glands often escape complete immune-mediated clearance due to immune privilege status of the salivary glands and the development of systemic oral tolerance to oral antigens. To further analyze the role in SG localized SARS-CoV-2 infection, we will 1) develop a murine model of SARS-CoV-2 spike protein expression in salivary gland tissue to evaluate release of antigen into saliva and capacity to trigger the development of oral tolerance, 2) measure immunization-mediated clearance of SARS-CoV-2 antigens from SG tissue and 3) evaluate the impact of oral antigen exposure on existing immunization efficacy and ability to support long lasting immunity. Data obtained from the proposed studies will further define the role of SG localized SARS-CoV-2 infections and potential avenues for development of oral tolerance-based therapies.