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

唾液腺局部 SARS-CoV-2 感染在口腔耐受中的作用

基本信息

批准号：
10239756
负责人：
Melodie Lynn Weller
金额：
$ 22.88万
依托单位：
UNIVERSITY OF UTAH
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-01 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10239756
关键词：
2019-nCoV ACE2 Acute Antibodies Antigens Applications Grants Blood COVID-19 COVID-19 patient Chronic Clinical Research Coronavirus Cytomegalovirus Data Development Diagnosis Disease Dose Exposure to Focal Infection Future Human Immune Immunity Immunization Immunize Individual Infection Inflammation Lymphocyte Maintenance Measures Mediating Modeling Monitor Mus Oral Patients Production Protocols documentation Recombinants Reporting Role SARS coronavirus SARS-CoV-2 antigen SARS-CoV-2 infection SARS-CoV-2 spike protein Saliva Salivary Gland Tissue Salivary Glands Serology Spleen Syndrome T-Cell Proliferation Tissues United States Vaccines Viral Viral Antigens Viral Proteins Virus Virus Diseases adeno-associated viral vector base cytokine design gland development lymph nodes mouse model neutralizing antibody novel novel coronavirus oral tolerance pathogen patient population prevent protein expression receptor relapse risk respiratory tool vaccine efficacy vaccine-induced immunity

项目摘要

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.

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。