FcRn-Targeted Mucosal Vaccination Against Influenza Infections

针对流感感染的 FcRn 靶向粘膜疫苗接种

• 批准号: 10397578
• 负责人: XIAOPING ZHU
• 金额: $ 54.21万
• 依托单位: UNIV OF MARYLAND, COLLEGE PARK
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-14 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10397578
• 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; 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; Lead; Lung; M2 protein; Measures; Mediating; Modeling; Morbidity - disease rate; Mucosal Immunity; Mucous Membrane; Mus; Muscle; Nature; Neuraminidase; Nucleoproteins; Persons; Plasma Cells; Population; Pregnant Women; Proteins; Public Health; Pulmonary Inflammation; Pulmonary Pathology; Respiratory Mucosa; Respiratory System; Route; Safety; Seasons; Secondary to; Severity of illness; Skin; T cell response; T memory cell; T-Lymphocyte; Technology; Testing; Tissues; Update; Vaccine Antigen; Vaccine Production; Vaccines; Viral Antigens; Virus; Virus Diseases; aged; airway inflammation; base; 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; universal influenza vaccine; vaccination strategy; vaccine delivery; vaccine efficacy

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.

项目摘要 甲型流感病毒直接引起急性呼吸道炎症或易发生继发性 细菌感染。高度抗原性变异是反复感染的主要原因。 当前疫苗诱导的免疫保护是紧密针对毒株的，因此疫苗需要 每年更新；毒株匹配疫苗的可用性通常落后于这些 抗原性变化。因此，扩大流感疫苗的接种范围是一大目标 使用保守的流感病毒抗原希望诱导交叉保护的效果 对抗原性相似和不同的病毒具有免疫力。因为流感病毒会引发 其感染在呼吸道，重要的是诱导交叉保护和持久 粘膜免疫。然而，我们通过粘膜安全运送疫苗抗原的能力 产生有效的粘膜免疫的屏障非常有限，特别是对老年人来说， 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)抗原可产生有效的免疫反应 抗粘膜感染。这些发现使我们进一步研究FcRN介导的 流感抗原的呼吸道输送可诱导交叉保护性免疫。因此，我们将 用保守的流感抗原经鼻免疫小鼠和雪貂，这些抗原的靶向是 FcRN，并充分分析它们的粘膜和系统免疫反应。最后，接种了疫苗的 老鼠和雪貂将受到抗原性相似或不相似的病毒的挑战 评估保护或交叉保护的效果。从这项研究中获得的知识将 对人类和动物的公共健康很重要。