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: 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
• 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

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型流感病毒感染在世界范围内引起显著的发病率和死亡率，并构成重大的公共卫生问题。 问题，特别是在幼儿和婴儿。B型流感病毒约占流行性感冒病毒的25%， 流感病毒在流行病中起重要作用，但导致高达38%的流感相关儿科死亡。目前行货 灭活疫苗不诱导广泛的保护，这是由于病毒血凝素在 这些疫苗的重点。在这个项目中，我们的目标是调查流感B的交叉保护， 病毒神经氨酸酶为基础的抗原可以赋予和他们的影响传播豚鼠模型。 此外，我们将探索这种广泛保护性免疫的表位特异性。初步数据显示 接种B-神经氨酸酶可以完全保护小鼠免于发病和死亡， 用抗原性不同的流感B病毒攻击。更多的证据来自广泛的保护性 结合并抑制1940年至2013年期间抗原性不同的B型流感病毒分离株的抗体。 与甲型流感病毒不同，B型流感病毒缺乏动物宿主，仅在人类中传播。 理论上，一种具有广泛保护性的疫苗加上高疫苗接种率， 根除B型流感病毒。这将导致全球负担减少约25%， 流感病毒感染。一种基于神经氨酸酶的免疫原，与免疫后给予或作为加强剂， 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。