Preclinical evaluation of manufacturable SARS-CoV-2 spike virus-like particles produced in Chinese Hamster Ovary cells

作者：Sergio P. Alpuche‐Lazcano, Matthew Stuible, Bassel Akache, Anh Tran, John F. Kelly, Sabahudin Hrapovic, Anna Robotham, Arsalan S. Haqqani, Alexandra T. Star, Tyler M. Renner, Julie Blouin, Jean‐Sébastien Maltais, Brian Cass, Kai Cui, Jae‐Young Cho, Xinyu Wang, Daria Zoubchenok, Renu Dudani, Diana Duque, Michael J. McCluskie, Yves Durocher · 发表于：Communications Medicine · 年份：2023 · DOI：10.1038/s43856-023-00340-7 · 被引用次数：18 · 研究领域：Viral Infectious Diseases and Gene Expression in Insects、SARS-CoV-2 and COVID-19 Research、Transgenic Plants and Applications

BACKGROUND: As the COVID-19 pandemic continues to evolve, novel vaccines need to be developed that are readily manufacturable and provide clinical efficacy against emerging SARS-CoV-2 variants. Virus-like particles (VLPs) presenting the spike antigen at their surface offer remarkable benefits over other vaccine antigen formats; however, current SARS-CoV-2 VLP vaccines candidates in clinical development suffer from challenges including low volumetric productivity, poor spike antigen density, expression platform-driven divergent protein glycosylation and complex upstream/downstream processing requirements. Despite their extensive use for therapeutic protein manufacturing and proven ability to produce enveloped VLPs, Chinese Hamster Ovary (CHO) cells are rarely used for the commercial production of VLP-based vaccines. METHODS: Using CHO cells, we aimed to produce VLPs displaying the full-length SARS-CoV-2 spike. Affinity chromatography was used to capture VLPs released in the culture medium from engineered CHO cells expressing spike. The structure, protein content, and glycosylation of spikes in VLPs were characterized by several biochemical and biophysical methods. In vivo, the generation of neutralizing antibodies and protection against SARS-CoV-2 infection was tested in mouse and hamster models. RESULTS: We demonstrate that spike overexpression in CHO cells is sufficient by itself to generate high VLP titers. These VLPs are evocative of the native virus but with at least thre...