Broad humoral protection induced by influenza B neuraminidase-based immunogens

 描述（由申请方提供）：B型流感病毒感染在全球范围内引起显著的发病率和死亡率，并构成主要的公共卫生问题，特别是在幼儿和婴儿中。B型流感病毒占流行性流感病毒的约25%，但导致高达38%的流感相关儿科死亡。目前许可的灭活疫苗不诱导广泛的保护，因为这些疫苗所关注的病毒血凝素的快速抗原漂移。在这个项目中，我们的目标是调查的交叉保护，流感B病毒的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，当用抗原性不同的流感B病毒攻击时，用B-神经氨酸酶接种可以完全保护小鼠免于发病和死亡。更多的证据来自广泛的保护性抗体，这些抗体结合并抑制1940年至2013年期间抗原性不同的B流感病毒分离株。流感 B病毒--与A型流感病毒相反--缺乏动物宿主，只在人类中传播。广泛保护的疫苗结合高疫苗接种率理论上可用于根除B型流感病毒。这将使流感病毒感染造成的全球负担减少约25%。一种基于神经氨酸酶的免疫原与常规三价流感病毒疫苗联合使用或在常规三价流感病毒疫苗后作为加强剂使用，可能是实现这一目标所需的金弹。

 DESCRIPTION (provided by applicant): 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.