Broad humoral protection induced by influenza B neuraminidase-based immunogens

 描述(由申请人提供)：B型流感病毒感染在世界范围内导致严重的发病率和死亡率，并构成一个重大的公共卫生问题，特别是在幼儿和婴儿中。B型流感病毒约占疫情中流行的流感病毒的25%，但在与流感相关的儿科死亡病例中占38%。目前获得许可的灭活疫苗由于病毒血凝素的快速抗原性漂移而不能产生广泛的保护作用，这些疫苗主要针对的是病毒血凝素。本研究旨在探讨乙型流感病毒神经氨酸酶抗原在豚鼠模型中的交叉保护作用及其对病毒传播的影响。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，接种B-神经氨酸酶疫苗可以完全保护小鼠在受到抗原性不同的B型流感病毒攻击时免受发病率和死亡率的影响。更多的证据来自广泛的保护性抗体，这些抗体结合和抑制1940年至2013年期间不同的抗原性B型流感病毒分离株。流感 与甲型流感病毒不同，B型病毒缺乏动物宿主，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%。以神经氨酸酶为基础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增强剂使用，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.