UNDERSTANDING THE MECHANISM OF YELLOW FEVER 17D VACCINE EFFICACY: AN IMMUNO-STRUCTURAL APPROACH TOWARDS THE DESIGN OF A PAN-FLAVIVIRUS VACCINE

在全球化经济中，黄热病病毒在非洲重新出现，给亚洲未受影响的地区带来了很大的蔓延风险。尽管YF 17 D疫苗可用，但其供应量低以及我们对病毒生物学和疫苗免疫原性的认识不足，使我们有可能对感染的指数级传播毫无准备。使用专注于病毒包膜蛋白的结构方法，我们最近发现了YF野生型和疫苗株之间宿主-病毒相互作用的重要差异。我们的两国联盟提出了一种基于不同专业知识的多学科方法，以评估：1）相关细胞中的病毒进入和抗原呈递，2）对疫苗和野生型毒株的差异细胞应答，以及3）接种疫苗的人类和野生型感染或接种疫苗的灵长类动物中的B细胞受体和抗体库。了解YF 17 D免疫原性的机制将允许设计针对泛黄病毒疫苗的新方法。

Yellow fever virus re-emergence in Africa in a globalized economy presents a significant risk of spillover to unaffected areas in Asia. Despite the availability of the YF17D vaccine, its low supply and our poor insight into viral biology and vaccine immunogenicity bear the risk to be unprepared for an exponential spread of infection. Using a structural approach focused on the viral envelope protein, we recently discovered important differences in the host-virus interaction between YF wild type and vaccine strains. Our bi-national consortium proposes a multi-disciplinary approach based on diverse expertise to assess: 1) viral entry and antigen presentation in relevant cells, 2) the differential cellular response to vaccine and wild type strains, and 3) the B-cell receptor and antibody repertoire in both vaccinated humans and wild type-infected or vaccinated primates. Understanding the mechanism of YF17D immunogenicity will allow designing new approaches towards a pan-flavivirus vaccine.