FcRn-Targeted Mucosal Vaccination Against Influenza Infections

针对流感感染的 FcRn 靶向粘膜疫苗接种

基本信息

批准号：
10599875
负责人：
XIAOPING ZHU
金额：
$ 53.91万
依托单位：
UNIV OF MARYLAND, COLLEGE PARK
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-05-14 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10599875
关键词：
Acute Adjuvant Adult Animals Antibodies Antibody Formation Antibody Response Antibody-mediated protection Antigen Targeting Antigenic Variation Antigens Attenuated Attenuated Vaccines Bacterial Infections Binding Sites Bone Marrow Capsid Proteins Cell secretion Cellular Immunity Clinical Developed Countries Development Disease Elderly Engineering Epithelial Cells Exposure to Fc Receptor Ferrets Generations Goals Half-Life Helper-Inducer T-Lymphocyte Hemagglutinin Human Immune Immune response Immunity Immunization Immunize Immunoglobulin G Infection Infectious Agent Influenza Influenza A virus Influenza vaccination Knockout Mice Knowledge Lung M2 protein Measures Mediating Modeling Morbidity - disease rate Mucosal Immunity Mucous Membrane Mus Muscle Nature Neuraminidase Nucleoproteins Persons Plasma Cells Population Predisposition Pregnant Women Proteins Public Health Pulmonary Inflammation Pulmonary Pathology Respiratory Mucosa Respiratory System Route Safety Secondary to Severity of illness Skin T cell response T-Lymphocyte Testing Update Vaccine Antigen Vaccine Production Vaccines Viral Antigens Virus Virus Diseases aged airway inflammation biosafety level 3 facility cross immunity design efficacy evaluation flu high risk population influenza infection influenza virus strain influenza virus vaccine influenzavirus mortality mucosal vaccination mucosal vaccine mutant neonatal Fc receptor neutralizing antibody parenteral administration pathogen respiratory seasonal influenza technology platform tissue resident memory T cell transmission process universal influenza vaccine vaccination strategy vaccine delivery vaccine efficacy

项目摘要

Project Summary Influenza A viruses directly cause acute airway inflammation or predispose to secondary bacterial infections. A highly antigenic variability is the main reason for repeated infections. Immune protection induced by current vaccines is closely strain-specific and the vaccines need to be updated each year; the availability of strain-matched vaccines usually lags behind these antigenic changes. Therefore, it is a major goal to broaden the range of influenza vaccine efficacy by using the conserved influenza virus antigens in the hope of inducing cross-protective immunity against both antigenically similar and different viruses. Since influenza virus initiates its infection at respiratory tract, it is important to induce the cross-protective and long-lasting mucosal immunity. However, our ability to safely deliver vaccine antigens across the mucosal barrier for generation of an effective mucosal immunity is very limited, especially for the elderly, young people and pregnant women. We recently found that the mucosal delivery of vaccine antigens by the neonatal Fc Receptor (FcRn) can engender effective immune responses against mucosal infections. These findings lead us to further examine whether FcRn-mediated airway delivery of the influenza antigens induces cross-protective immunity. Therefore, we will intranasally immunize mice and ferret with the conserved influenza antigens that are targeting to FcRn and fully analyze their mucosal and systemic immune responses. Finally, the immunized mice and the ferret will be challenged with virus antigenically similar or dissimilar viruses to evaluate the efficacy of protection or cross protection. The knowledge gained from this study will be important for public health in humans and animals.

项目概要甲型流感病毒直接引起急性气道炎症或诱发继发性炎症细菌感染。高度的抗原变异性是重复感染的主要原因。当前疫苗诱导的免疫保护具有紧密的毒株特异性，并且疫苗需要每年更新一次；毒株匹配疫苗的可用性通常落后于这些疫苗抗原改变。因此，扩大流感疫苗的范围是一个主要目标通过使用保守的流感病毒抗原以期诱导交叉保护的功效针对抗原相似和不同病毒的免疫力。自流感病毒爆发以来其呼吸道感染，诱导交叉保护和持久很重要粘膜免疫。然而，我们通过粘膜安全递送疫苗抗原的能力产生有效粘膜免疫的屏障非常有限，特别是对于老年人来说，年轻人和孕妇。我们最近发现疫苗的粘膜递送新生儿 Fc 受体 (FcRn) 的抗原可以产生有效的免疫反应对抗粘膜感染。这些发现促使我们进一步研究 FcRn 介导的流感抗原的气道输送诱导交叉保护性免疫。因此，我们将用保守的流感抗原对小鼠和雪貂进行鼻内免疫，这些抗原的目标是 FcRn 并全面分析其粘膜和全身免疫反应。最后，免疫小鼠和雪貂将受到抗原相似或不相似的病毒的攻击评估保护或交叉保护的功效。从这项研究中获得的知识将对人类和动物的公共卫生很重要。