Broad humoral protection induced by influenza B neuraminidase-based immunogens

基于乙型流感神经氨酸酶的免疫原诱导广泛的体液保护

基本信息

批准号：
9301332
负责人：
Florian Krammer
金额：
$ 42.38万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-06-20 至 2021-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9301332
关键词：
Animal Model Animals Antibodies Antibody Response Antigens Attenuated Binding Biochemical Cavia Cessation of life Child Childhood Data Disease Epidemic Epitopes Future Goals Hemagglutinin Human Immune response Immunity Inactivated Vaccines Infant Infection Influenza Influenza A virus Influenza B Virus Knowledge Maps Mediating Membrane Glycoproteins Mind Modeling Monoclonal Antibodies Morbidity - disease rate Mus Neuraminidase Pattern Population Prevalence Prevention Property Prophylactic treatment Proteins Public Health Recombinants Respiratory Syncytial Virus Infections Risk Route Smallpox Specificity Testing Therapeutic Vaccination Vaccine Antigen Vaccine Design Vaccines Viral Hemagglutinins Virus Virus Diseases base cross reactivity design experimental study flu transmission influenza virus vaccine influenzavirus insight mortality mouse model prophylactic success tool transmission process viral transmission

Animal Model Animals Antibodies Antibody Response Antigens Attenuated Binding Biochemical Cavia Cessation of life Child Childhood Data Disease Epidemic Epitopes Future Goals Hemagglutinin Human Immune response Immunity Inactivated Vaccines Infant Infection Influenza Influenza A virus Influenza B Virus Knowledge Maps Mediating Membrane Glycoproteins Mind Modeling Monoclonal Antibodies Morbidity - disease rate Mus Neuraminidase Pattern Population Prevalence Prevention Property Prophylactic treatment Proteins Public Health Recombinants Respiratory Syncytial Virus Infections Risk Route Smallpox Specificity Testing Therapeutic Vaccination Vaccine Antigen Vaccine Design Vaccines Viral Hemagglutinins Virus Virus Diseases base cross reactivity design experimental study flu transmission influenza virus vaccine influenzavirus insight mortality mouse model prophylactic success tool transmission process viral transmission

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项目摘要

Influenza B virus infections cause significant morbidity and mortality worldwide and pose a major public health problem, specifically in young children and infants. Influenza B viruses represent about 25% of circulating influenza viruses in an epidemic but cause up to 38% of influenza-related pediatric deaths. Currently licensed inactivated vaccines do not induce broad protection due to the fast antigenic drift of the viral hemagglutinin on which these vaccines focus. In this project we are aiming to investigate the cross-protection that influenza B virus neuraminidase-based antigens can confer and their effect on transmission in the guinea pig model. Furthermore, we will explore the epitope specificity of this broadly protective immunity. Preliminary data show that vaccination with B-neuraminidase can protect mice completely from morbidity and mortality when challenged with antigenically distinct influenza B viruses. More evidence comes from broadly protective antibodies that bind and inhibit antigenically distinct influenza B virus isolates spanning from 1940 to 2013. Influenza B viruses - in contrast to influenza A viruses - lack an animal reservoir and only circulate in humans. A broadly protective vaccine in combination with a high vaccination rate could theoretically be used to eradicate influenza B virus. This would result in an approximately 25% decrease in the global burden caused by influenza virus infections. A neuramindase-based immunogen given in combination with or as booster after regular trivalent influenza virus vaccine could be the golden bullet needed to achieve this goal.

流感B病毒感染引起了全世界的显着发病率和死亡率，并构成了主要的公共卫生问题，特别是在幼儿和婴儿中。流感B病毒约占循环的25％流行病中的流感病毒，但最多可导致38％的与流感相关的儿科死亡。目前已获得许可灭活的疫苗不会因病毒性血凝素快速漂移而引起广泛的保护这些疫苗的重点。在这个项目中，我们旨在调查流感B的交叉保护基于病毒神经酶酶的抗原及其对豚鼠模型中传播的影响。此外，我们将探讨这种广泛保护性免疫的表位特异性。初步数据显示当B-神经胺酶接种时，可以完全保护小鼠免受发病率和死亡率受到抗原不同的流感B病毒的挑战。更多证据来自广泛的保护性结合并抑制从1940年至2013年的抗原不同的流感B病毒分离株结合并抑制抗原不同的抗原抗体。流感B病毒 - 与流感A病毒相比 - 缺乏动物储层，仅在人类中循环。从理论上讲，可以将广泛的保护性疫苗与高疫苗接种率结合使用根除流感B病毒。这将导致造成的全球负担约25％通过流感病毒感染。基于神经素酶的免疫原与在定期的三价流感病毒疫苗可能是实现这一目标所需的金色子弹。