Bourigault Léa, Bresson Corinne, Jean Christian, Chevalard Christophe, Kloutz Mathilde, Soulet Damien, Pelissier Fleurine, Richard Stéphanie, Bassard Isabelle, Sève Nicolas, Charretier Cédric, Pain Bertrand
University of Lyon, Université Lyon 1, INSERM, INRAE, Stem Cell and Brain Research Institute U1208, Bron, France.
Sanofi Vaccines, VCDS Global Bioprocess Development, Marcy L'Etoile, France.
NPJ Vaccines. 2025 Jun 5;10(1):114. doi: 10.1038/s41541-025-01157-2.
Vero cells, as approved by the World Health Organization, have been the most commonly used continuous cell line for viral vaccine production over the last 25 years, but their adherent phenotype continues to limit productivity. Adapting to a suspension culture would overcome this restriction and reduce production costs. First, a Vero suspension isolate was obtained and metabolically characterized. Second, RNA sequencing analysis was used to identify differentially expressed genes between adherent and suspension cells, which revealed complete downregulation of adhesion and matrix-associated genes. Additionally, signaling pathways involving Wnt and other tyrosine kinase receptors were identified as potential leads for growth optimization. In particular, supplementation with fibroblast growth factor 2 allowed for a 20% increase in cell density. Finally, a comparative viral productivity assay revealed a 30% increase in poliovirus production in suspension Vero cells compared to adherent cells depending on the serotype, as well as a 140% increase in respiratory syncytial virus production and a 150% increase in yellow fever virus production. This work establishes the potential of the suspension Vero cell line as a new cell platform for viral vaccine production.
在过去25年里,经世界卫生组织批准,Vero细胞一直是病毒疫苗生产中最常用的连续细胞系,但其贴壁表型持续限制着生产效率。适应悬浮培养将克服这一限制并降低生产成本。首先,获得了一株Vero悬浮分离株并对其进行代谢特征分析。其次,利用RNA测序分析来鉴定贴壁细胞和悬浮细胞之间差异表达的基因,结果显示粘附和基质相关基因完全下调。此外,涉及Wnt和其他酪氨酸激酶受体的信号通路被确定为生长优化的潜在线索。特别是,添加成纤维细胞生长因子2可使细胞密度提高20%。最后,一项比较病毒生产能力的试验表明,根据血清型不同,悬浮Vero细胞生产脊髓灰质炎病毒的能力比贴壁细胞提高了30%,呼吸道合胞病毒产量提高了140%,黄热病毒产量提高了150%。这项工作确立了悬浮Vero细胞系作为病毒疫苗生产新细胞平台的潜力。