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

项目综述|唾液腺局部感染SARS-CoV-2在口服耐受和免疫效果中的作用 美国已有500多万人被诊断出患有系统性急性呼吸综合征 冠状病毒-2，SARS-CoV-2，感染1。一个主要的悬而未决的问题是，患者是否从 无论是SARS-CoV-2还是对SARS-CoV-2免疫，都会产生持久的免疫。有关新冠肺炎的早期报道称 概述了唾液腺(SG)定位的SARS-CoV-2在新冠肺炎症状发展中的潜在作用。 能够感染唾液腺的病毒通常由于免疫而逃脱免疫介导的完全清除。 唾液腺的特权状态与系统性口服抗原耐受性的发展。进一步分析 SG在SARS-CoV-2局部化感染中的作用，我们将1)建立SARS-CoV-2刺突蛋白的小鼠模型 在唾液腺组织中表达以评估唾液中抗原的释放和触发口腔发育的能力 耐受性，2)检测免疫介导的SARS-CoV-2抗原从SG组织中的清除，3)评估其影响 口服抗原暴露对现有免疫效力和支持长期免疫的能力的影响。获得的数据 来自拟议的研究将进一步确定SG本地化SARS-CoV-2感染的作用和潜在的途径 发展以口服耐受性为基础的治疗方法。

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.