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: 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
• 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

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气道炎症或易引起继发性 细菌感染高度抗原变异性是反复感染的主要原因。 现有疫苗诱导的免疫保护具有高度的毒株特异性， 每年更新;菌株匹配疫苗的可用性通常滞后于这些 抗原变化因此，拓宽流感疫苗的接种范围是一个主要目标 通过使用保守的流感病毒抗原，希望诱导交叉保护， 对抗原相似和不同病毒的免疫力。自从流感病毒开始 其在呼吸道的感染，重要的是诱导交叉保护和持久的 粘膜免疫然而，我们能够安全地将疫苗抗原穿过粘膜， 产生有效粘膜免疫的屏障非常有限，特别是对于老年人， 年轻人和孕妇。我们最近发现粘膜递送疫苗 新生儿Fc受体（FcRn）介导的抗原可产生有效的免疫应答 对抗粘膜感染。这些发现使我们进一步研究FcRn介导的 流感抗原的气道递送诱导交叉保护性免疫。所以我们会 鼻内免疫小鼠和雪貂与保守的流感抗原，靶向 FcRn，并充分分析其粘膜和全身免疫反应。最后，免疫者 小鼠和雪貂将用抗原性相似或不相似的病毒进行攻击， 评估保护或交叉保护的有效性。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。