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

项目概述：用于快速VLP疫苗开发的模块化平台， 为应对SARS-CoV-2大流行而制造 该提案旨在设计、开发和制造病毒样颗粒（VLP）疫苗， SARS-CoV-2和整个工作中开发的技术可以应用于加速 应对未来流行病的疫苗管道。我们将构建一个VLP表达系统， 在HEK 293主机中有效地产生一致的VLP产物。这个生产平台是 设计成使得SARS-CoV-2的刺突蛋白特征可以容易地被修饰， 允许疫苗响应于关键的病毒突变而被修改。产生的VLP 生产系统将按比例扩大，并用于先进工艺的开发。VLP将 可以在灌注模式下产生，从而产生具有高产物产率的更具生产力的平台。 VLP疫苗的灌注处理的成功实施将使其他基于VLP的疫苗成为可能。 使用更小的设施占地面积更快地制造产品， 生产，以满足全球需求。先进的过程分析技术（PAT） 用于充分表征工艺和产品，建立基线关键质量 属性（CQA）配置文件，以确保产品始终安全有效。期间收集的数据 工艺开发将用于生成先进的工艺模型和鲁棒控制 VLP疫苗的最佳生产策略。这一高度合作的努力将 展示了一种快速、精简的VLP疫苗开发和生产工艺， 这可以减少疫苗推出的时间，因为新的冠状病毒，冠状病毒株， 其他病毒病原体出现。这里提出的工作不仅能产生疫苗 SARS-CoV-2的候选人，但本文所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.