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.

乙型流感病毒感染在全球范围内造成显着的发病率和死亡率，并构成重大公共卫生问题 问题，特别是幼儿和婴儿。乙型流感病毒约占循环病毒的 25% 流感病毒是一种流行病，但导致高达 38% 的流感相关儿童死亡。目前已获得许可 由于病毒血凝素的快速抗原漂移，灭活疫苗不会产生广泛的保护。 这些疫苗的重点。在这个项目中，我们的目标是研究乙型流感病毒的交叉保护作用 基于病毒神经氨酸酶的抗原可以赋予豚鼠模型中的传播及其影响。 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 接种 B-神经氨酸酶疫苗可以完全保护小鼠免受发病和死亡的影响 受到抗原性不同的乙型流感病毒的攻击。更多证据来自广泛的保护 结合并抑制 1940 年至 2013 年抗原上不同的乙型流感病毒分离株的抗体。 与甲型流感病毒相比，乙型流感病毒缺乏动物宿主，仅在人类中传播。 理论上，具有广泛保护性的疫苗与高疫苗接种率相结合可用于 消灭乙型流感病毒。这将使全球负担减少约 25% 由流感病毒感染引起。基于神经氨酸酶的免疫原与联合给药或作为加强剂给药后给予 常规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