Intranasal, rapid-acting vaccine for all seasonal and pandemic influenza viruses

项目概述世界各地的研究人员一直在努力开发一种通用的流感疫苗，但尚未取得突破。FlUniversal并不是“又一个代价高昂的全球流感项目”。这是一个创造真正的通用流感疫苗的机会，它将为快速、高效的疫苗开发设定标准，并产生开发下一代疫苗的技术诀窍和工具。我们计划利用我们对流感感染和免疫的分子机制的日益加深的了解来开发一种对所有流感病毒株有效的疫苗。我们的创新使用了转基因流感毒株，在优质增强方案中鼻腔给药。这种方法迅速在鼻道中诱导干扰素和广泛的交叉中和抗体，并针对保守的HA柄产生全身免疫反应。在雪貂身上证明了普遍保护的概念；我们现在建议在人类身上展示概念证明。之前的临床研究证实了该药在人体内的安全性和免疫原性。这些菌株是在Vero细胞中高效生产的。FLUniversal的目标与预期结果一致：临床前模型的全面免疫学评估，人类挑战模型的开发，以及协助医疗保健利益相关者关于支持疫苗开发的决策。该联盟成员在临床前模型、临床试验、免疫学和有效化验方面的世界领先专业知识将提供关于保护机制的宝贵见解。拟议的临床研究将提供关键的临床概念证据，推动疫苗走向商业化。

Project summary Researchers worldwide have been working to develop a universal flu vaccine, but no breakthrough has yet been achieved. FLUniversal is not "another costly universal flu project". It is an opportunity to create a genuine universal flu vaccine that will set the standard for rapid, efficient vaccine development, and generate know-how and tools to develop next-generation vaccines. We plan to exploit our increased understanding of molecular mechanisms of influenza infection and immunity to develop a vaccine effective against all flu virus strains. Our innovation uses genetically modified flu strains administered intranasally in a prime-boost regimen. This approach rapidly induces interferon and broadly cross-neutralising antibodies in the nasal passages and a systemic immune response directed to the conserved HA stalk. Proof of concept for universal protection was demonstrated in the ferret; we propose now to show proof of concept in humans. Previous clinical studies established safety and immunogenicity in humans. The strains are efficiently produced in Vero cells. FLUniversal's objectives align with the Expected Outcomes: comprehensive immunological assessment of preclinical models, development of a human challenge model, and assisting healthcare stakeholders’ decision-making about support for vaccine development. Consortium members’ world-leading expertise in preclinical models, clinical trials, immunology and validated assays will provide valuable insights on mechanisms of protection. Proposed clinical studies will provide crucial clinical proof of concept to advance the vaccine toward commercialisation.