Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China.
School of Chemical and Biomolecular Engineering, University of Sydney, Sydney, 2008, Australia.
Int J Biol Sci. 2022 May 9;18(8):3405-3420. doi: 10.7150/ijbs.71983. eCollection 2022.
Vaccination still remains as the most effective approach for preventing infectious diseases such as those caused by virus infection, with cell-based vaccine manufacturing being one flexible solution regarding the spectrum of infectious disorders it can prevent. Rapid cell-based virus propagation can enable high yield of vaccines against viral diseases that may offer critical values in the industry when handling emergent situations such as the ongoing viral disease pandemic. Through investigating the phenomenon and biological mechanism underlying redox-triggered cell survival towards enhanced viral particle production, this study explores novel strategies for improved yield of viral particles at a reduced cost to meet the increasing demand on cell-based vaccine manufacturing against viral diseases. We found in this study that cold atmospheric plasma (CAP), composed of multiple reactive oxygen and nitrogen species including HO, could effectively enhance virus replication via triggering cell mitophagy that was dynamically modulated by the p-EGFR(Tyr1068)/p-Drp1(Ser616) axis using IBRV and MDBK as the virus and cell models, respectively; and removing HO can further enhance virus yield via releasing cells from excessive G/G cell cycle arrest. The observed efficacy of CAP was extended to other viruses such as CDV and CPV. This study provides experimental evidences supporting the use of CAP as a modulator of cell survival including mitophagy and mitochondria dynamics, and makes CAP an interesting and promising tool for enhancing the yield of viral vaccines if translated into the industry.
疫苗接种仍然是预防传染病的最有效方法，例如由病毒感染引起的传染病，而基于细胞的疫苗制造是一种灵活的解决方案，可以预防多种传染病。快速的基于细胞的病毒繁殖可以提高针对病毒性疾病的疫苗产量，这在处理紧急情况（如当前的病毒性疾病大流行）时可能具有重要的行业价值。 通过研究氧化还原触发细胞存活以增强病毒颗粒产生的现象和生物学机制，本研究探索了提高病毒颗粒产量的新策略，以降低成本，满足针对病毒性疾病的基于细胞的疫苗制造的需求不断增加。 在这项研究中，我们发现冷等离子体（CAP）由多种活性氧和氮物种组成，包括 HO，可以通过触发细胞自噬来有效增强病毒复制，细胞自噬由 p-EGFR（Tyr1068）/p-Drp1（Ser616）轴动态调节，分别使用 IBRV 和 MDBK 作为病毒和细胞模型；去除 HO 可以通过使细胞摆脱过度的 G/G 细胞周期阻滞来进一步提高病毒产量。CAP 的观察到的功效扩展到其他病毒，如 CDV 和 CPV。 本研究提供了支持使用 CAP 作为细胞存活调节剂（包括自噬和线粒体动力学）的实验证据，如果将其转化为工业用途，CAP 将成为增强病毒疫苗产量的有趣且有前途的工具。
