Advanced manufacturing technology of virus like particles for vaccination

疫苗接种仍然是控制疾病和有助于降低保健费用的最成功的医疗干预措施之一。在新型的抗原呈递方法中，病毒样颗粒（VLP）疫苗是应对大流行性流感病毒株持续威胁的最有前途的方法之一。在可用于生产VLP的平台中，昆虫细胞生产平台在使用该技术生产的疫苗获得许可后已获得行业的显著关注和接受。该项目采用系统方法（在分子和全球层面：从基因到代谢组，从细胞设计到产品纯化），在制造过程中对感兴趣的材料（材料系统接受的主题：病毒样颗粒）进行研究。这项工作在商业化方面处于有利地位，得到了以下方面的支持：Biogro Technologies，该公司对开发用于昆虫细胞技术平台的完全限定培养基感兴趣;和Chenomx Inc.，他们希望开发算法来自动分析NMR光谱，使他们的平台适合作为生物制造中使用的过程分析技术。更具体地说，这项工作将解决与使用昆虫细胞/杆状病毒表达系统生产包膜VLP相关的关键挑战。该战略项目的总体目标是开发一种稳健且高产的昆虫细胞培养工艺，用于生产流感病毒VLP，具体目标是大规模工业化生产。为实现这一目标：1）将开发新的昆虫细胞培养表达系统; 2）将通过合理的培养基设计和工艺强化优化VLP产量，目标是在现有产量的基础上提高10倍; 3）将开发新的纯化方法和新的工艺分析技术;以及4）将记录产品的工艺和质量属性，以支持技术转让。总的来说，该项目将有助于建设加拿大的生物制造能力，并最终提高加拿大应对新发传染病威胁的能力。

Vaccination remains one of the most successful medical interventions to control diseases and contribute to the reduction of health care costs. Among the novel antigen presentation approaches, Virus-Like Particle (VLP) vaccines are one of the most promising approaches to respond to the constant threat of pandemic influenza strains. Among the platforms that can be used for the production of VLPs, the insect cell production platform has been garnering significant attention and acceptance by industry following the licensing of vaccines manufactured using this technology. This project uses a systems approach (both at the molecular and global levels: from gene to metabolome and from cell design to product purification) to put research on a material of interest (material systems accepted topics: virus-like particles) in the context of a manufacturing process. The work is well positioned for commercialization given the support of: Biogro Technologies, which have interest in the development of a fully defined medium for the insect cell technology platform; and Chenomx Inc., which want to develop algorithms to automate profiling of NMR spectra to make their platform suitable as a Process Analytical Technology used in biomanufacturing. More specifically, this work will address critical challenges associated with the manufacturing of enveloped VLPs using an insect cell/baculovirus expression system. The overall objective of the strategic project is to develop a robust and high-yielding insect cell culture process for the production of influenza VLPs with the specific target of large-scale industrial manufacturing. To achieve this goal: 1) a new insect cell culture expression system will be developed; 2) VLP yield will be optimized through rational media design and process intensification targeting a ten-fold increase over the current yield; 3) new purification methods and new process analytical technologies will be developed; and 4) the process and the quality attributes of the product will be documented to support technology transfer. Overall this project will contribute to building biomanufacturing capacity in Canada and will ultimately lead to Canada's ability to respond to the threat of emerging infectious diseases.