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

• 批准号: 9927562
• 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
• 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/9927562
• 关键词: Animal Model; Animals; Antibodies; Antibody Response; Antigens; Attenuated; Binding; Biochemical; Cavia; Cessation of life; Child; Childhood; Data; Disease; Enzyme-Linked Immunosorbent Assay; 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

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.

B型流感病毒感染在全球范围内造成严重的发病率和死亡率，并构成主要的公共卫生 这一问题，特别是在幼儿和婴儿中。乙型流感病毒约占传播总数的25% 流感病毒在流行中，但在与流感相关的儿科死亡中，高达38%是由流感病毒引起的。目前已获得许可 灭活疫苗由于病毒血凝素的快速抗原漂移而不能产生广泛的保护作用 这些疫苗关注的是。在这个项目中，我们的目标是调查B型流感病毒的交叉保护 病毒神经氨酸酶抗原可在豚鼠模型中发挥作用及其对传播的影响。 此外，我们将探索这种广泛的保护性免疫的表位特异性。初步数据显示 在以下情况下，接种B-神经氨酸酶疫苗可以完全保护小鼠免受发病率和死亡率的影响 受到抗原性不同的B型流感病毒的挑战。更多的证据来自广泛的保护性 结合和抑制抗原性不同的B型流感病毒分离株的抗体，时间跨度从1940年到2013年。 与甲型流感病毒不同，B型流感病毒缺乏动物宿主，只在人类中传播。 一种具有广泛保护性的疫苗与高接种率相结合，理论上可以用来 根除乙型流感病毒。这将导致全球负担减少约25%。 被流感病毒感染。一种以神经氨酸酶为基础的免疫原，与后遗症联合使用或作为增强剂 常规的三价流感病毒疫苗可能是实现这一目标所需的金弹。

项目成果

Monoclonal Antibody Therapy Protects Pharmacologically Immunosuppressed Mice from Lethal Infection with Influenza B Virus.

单克隆抗体疗法可保护药理学免疫抑制的小鼠免受乙型流感病毒的致命感染。

• DOI: 10.1128/aac.00284-20
• 发表时间: 2020
• 期刊: Antimicrobial agents and chemotherapy
• 影响因子: 4.9
• 作者: Marathe,BindumadhavM;AsthagiriArunkumar,Guha;Vogel,Peter;Pascua,PhilippeNorielQ;Jones,Jeremy;Webby,RichardJ;Krammer,Florian;Govorkova,ElenaA
• 通讯作者: Govorkova,ElenaA