Department of Biotechnology, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand.
Sci Rep. 2024 Nov 18;14(1):28555. doi: 10.1038/s41598-024-79764-7.
Cervical cancer is the fourth most prevalent cancer among women globally, with Thai women ranking it as the third most common. At present, a prophylactic vaccine, containing virus-like particles (VLPs) of HPV L1 capsid protein, is widely recognized as one of the major prevention strategies for cervical cancer. Unfortunately, due to a low cross-protection among subtypes, protection against each HPV subtype requires vaccination with VLPs of that specific subtype. This study aimed to optimize the cultivation medium and conditions to maximize the volumetric yield of HPV52 L1 protein produced by the recombinant H. polymorpha HPV52. The results revealed that supplementation of a complex organic nitrogen source HySoy (at 10 g/L) into SYN6 medium resulted in a significantly higher specific HPV52 L1 yield and the maximum specific and volumetric HPV52 L1 protein yield were obtained at 30℃. In this study, the volumetric yield of HPV52 L1 could be increased from 50.9 mg/L in flask-scale cultivation to 2728 mg/L in High Cell Density Cultivation or HCDC (53-folds) with a significant improvement in terms of productivity, from 0.85 mg/L.h in flask-scale cultivation to 22.7 mg/L.h in HCDC (27-folds).
宫颈癌是全球女性第四大常见癌症，泰国女性将其列为第三大常见癌症。目前，一种包含 HPV L1 衣壳蛋白病毒样颗粒（VLPs）的预防性疫苗被广泛认为是预防宫颈癌的主要策略之一。不幸的是，由于各亚型之间的交叉保护作用较低，每种 HPV 亚型都需要接种该特定亚型的 VLPs 来预防。本研究旨在优化培养介质和条件，以最大限度地提高重组 H. polymorpha HPV52 产生的 HPV52 L1 蛋白的体积产率。结果表明，在 SYN6 培养基中添加复合有机氮源 HySoy（10 g/L）可显著提高 HPV52 L1 的比产率，在 30℃下可获得最大的 HPV52 L1 蛋白比产率和体积产率。在本研究中，HPV52 L1 的体积产率可以从摇瓶培养的 50.9 mg/L 提高到高密度细胞培养（HCDC）中的 2728 mg/L（53 倍），并且在生产力方面有显著提高，从摇瓶培养的 0.85 mg/L.h 提高到 HCDC 中的 22.7 mg/L.h（27 倍）。
