A modular platform for rapid VLP vaccine development and manufacturing for SARS-CoV-2 pandemic response

项目摘要：快速开发VLP疫苗的模块化平台和 SARS-CoV-2大流行应对措施的制造 该提案旨在设计、开发和制造一种病毒样颗粒(VLP)疫苗，用于 SARS-CoV-2，以及在整个工作中开发的技术可以应用于加速 疫苗流水线以应对未来的大流行。我们将生成一个VLP表达系统 在高效地创建一致VLP产品的HEK 293主机中。这个生产平台是 设计成SARS-CoV-2的刺突蛋白特征可以很容易地修改， 允许对疫苗进行修改以应对关键的病毒突变。由此产生的VLP 生产系统将扩大规模，用于先进工艺开发。VLP将 可在灌流模式下生成，从而获得更高效的平台和更高的产品产量。 VLP疫苗的灌流处理的成功实施将使基于VLP的其他 使用更小的设施占地面积更快地制造产品，从而实现快速 满足全球需求的制造业。高级过程分析技术(PAT)将 应用于全面描述过程和产品，建立基准关键质量 属性(CQA)配置文件，以确保产品始终安全有效。在此期间收集的数据 流程开发将用于生成先进的流程模型和稳健的控制 VLP疫苗最佳生产策略。这一高度协作的努力将 展示快速、简化的VLP疫苗开发和制造流程 这可以减少新冠状病毒、冠状病毒株和 其他病毒病原体也出现了。这里提出的工作不仅会产生疫苗 SARS-CoV-2的候选者，但这里描述的方法将产生一个平台 应对未来大流行或潜在病毒突变的过程。

Project Summary: A modular platform for rapid VLP vaccine development and manufacturing for SARS-CoV-2 pandemic response This proposal aims to design, develop, and manufacture a virus-like particle (VLP) vaccine for SARS-CoV-2, and the techniques developed throughout the work can be applied to accelerate the vaccine pipeline in response to future pandemics. We will generate a VLP expression system in a HEK 293 host that efficiently creates a consistent VLP product. This production platform was designed such that the Spike protein characteristic of SARS-CoV-2 can be easily modified, allowing the vaccine to be modified in response to critical viral mutations. The resulting VLP production system will be scaled up and used for advanced process development. The VLPs will be generated in perfusion mode, resulting in a more productive platform with a high product yield. Successful implementation of perfusion processing for a VLP vaccine will enable other VLP based products to be more rapidly manufactured using a smaller facility footprint, enabling rapid manufacturing to meet the global demand. Advanced process analytical technology (PAT) will be applied to fully characterize the process and product, establishing a baseline Critical Quality Attribute (CQA) profile to ensure a consistently safe and effective product. Data collected during process development will be used to generate advanced processing models and robust control strategies for optimal production of the VLP vaccine. This highly collaborative effort will demonstrate a rapid, streamlined VLP vaccine development and manufacturing process that can reduce the time to vaccine rollout as new coronaviruses, coronavirus strains, and other viral pathogens emerge. Not only will the work proposed here generate a vaccine candidate for SARS-CoV-2, but the methodology described herein will generate a platform process for response to future pandemics or potential viral mutations.