Chupin Caroline, Brun Pauline, Ray Marjorie, Mialon Chloé, Reitano Maëlle, Traversier Aurélien, Laurent Emilie, Goumaidi Abdelghafar, Fouret Julien, Paul Stéphane, Boukhvalova Marina, Yim Kevin, Blanco Jorge, Hamelin Marie-Eve, Boivin Guy, Rosa-Calatrava Manuel, Dubois Julia
International Research Laboratory RESPIVIR France - Canada, Centre Hospitalier Universitaire de Québec-Université Laval, Québec, Canada ; Centre International de Recherche en Infectiologie, Faculté de Médecine RTH Laennec, Université Claude Bernard Lyon 1, Université de Lyon, INSERM, CNRS, ENS de Lyon, 69008, Lyon, France.
CIRI, Centre International de Recherche en Infectiologie, Team VirPath, Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, F-15 69007, Lyon, France.
NPJ Vaccines. 2025 Aug 22;10(1):202. doi: 10.1038/s41541-025-01231-9.
Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) are the main etiologic agents of viral bronchiolitis and pneumonia in children and the elderly. As live-attenuated vaccines (LAV) can stimulate robust mucosal and cellular responses, we previously engineered an HMPV-based bivalent LAV Metavac®-RSV candidate and reported its capacity to protect mice against HMPV and RSV challenges after intranasal delivery. To progress towards clinical development, we identified a GMP-grade Vero cell platform as permissive and efficient to produce high yields of functional Metavac®-RSV, expressing both RSV and HMPV F antigen after several passages. Metavac®-RSV protected cotton rats against both HMPV and RSV challenges, significantly reducing viral replication in the respiratory airways and inducing high titers of neutralizing antibodies. Finally, we identified process parameters to scale-up the production process of Metavac®-RSV using Vero cells cultivated on microcarriers in a 2 L single-use stirred-tank bioreactor, with a scalable upstream production process amenable to industrial manufacturing.
呼吸道合胞病毒（RSV）和人偏肺病毒（HMPV）是引起儿童和老年人病毒性细支气管炎和肺炎的主要病原体。由于减毒活疫苗（LAV）可刺激强烈的黏膜和细胞反应，我们之前构建了一种基于HMPV的二价减毒活疫苗候选物Metavac®-RSV，并报道了其经鼻内接种后保护小鼠免受HMPV和RSV攻击的能力。为推进临床开发，我们确定了一个符合药品生产质量管理规范（GMP）级别的Vero细胞平台，该平台允许并高效生产高产量的功能性Metavac®-RSV，经过几代传代后可同时表达RSV和HMPV F抗原。Metavac®-RSV保护棉鼠免受HMPV和RSV攻击，显著减少呼吸道中的病毒复制，并诱导产生高滴度的中和抗体。最后，我们确定了工艺参数，以扩大在2升一次性搅拌罐生物反应器中使用微载体培养的Vero细胞生产Metavac®-RSV的生产工艺，其上游生产工艺具有可扩展性，适合工业制造。
