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比较在昆虫细胞和酵母细胞中产生的人乳头瘤病毒 16 型 L1 病毒样颗粒的大小分布和免疫原性。

Comparison of the size distributions and immunogenicity of human papillomavirus type 16 L1 virus-like particles produced in insect and yeast cells.

机构信息

Laboratory of Virology, College of Pharmacy, Chung-Ang University, 84 Heukseok-Ro, Dongjak-Gu, Seoul, 06974, South Korea.

出版信息

Arch Pharm Res. 2018 May;41(5):544-553. doi: 10.1007/s12272-018-1024-4. Epub 2018 Apr 10.

Abstract

Insect and yeast cells are considered the expression systems of choice for producing virus-like particles (VLPs), and numerous types of VLPs have been produced in these systems. However, previous studies were restricted to identifying the characteristics of individual VLP preparations. No direct comparison of the structures and immunogenic properties of insect and yeast-derived VLPs has so far been made. In the present study, the size distribution and immunogenic properties of human papillomavirus type 16 (HPV16) L1 VLPs produced in Spodoptera frugipedra-9 insect cells and Saccharomyces cerevisiae were compared. The insect cell-derived VLPs were larger than the yeast ones (P < 0.0001), with median sizes of 34 and 26 nm, respectively. In addition, the insect-derived VLPs appeared to be more diverse in size than the yeast-derived VLPs. Immunization of mice with 30 ng per dose of VLPs elicited 2.7- and 2.4-fold higher anti-HPV16 L1 IgG and anti-HPV16 neutralizing antibody titers than immunization with the same amounts of the yeast-derived VLPs after the 4th immunizations, respectively. Our results suggest that the choice of expression system critically affects the particle size and immunogenic property of HPV16 L1 VLPs.

摘要

昆虫和酵母细胞被认为是生产病毒样颗粒(VLPs)的首选表达系统,并且已经在这些系统中生产了许多类型的 VLPs。然而,以前的研究仅限于鉴定单个 VLP 制剂的特性。迄今为止,尚未对昆虫和酵母来源的 VLPs 的结构和免疫原性特性进行直接比较。在本研究中,比较了在 S. frugiperda-9 昆虫细胞和酿酒酵母中产生的人乳头瘤病毒 16 型(HPV16)L1 VLP 的大小分布和免疫原性。昆虫细胞来源的 VLPs 比酵母来源的 VLPs 更大(P < 0.0001),中位大小分别为 34 和 26nm。此外,与酵母来源的 VLPs 相比,昆虫来源的 VLPs 的大小似乎更加多样化。免疫小鼠 30ng 剂量的 VLPs 后,第 4 次免疫后,抗 HPV16 L1 IgG 和抗 HPV16 中和抗体滴度分别比免疫相同量的酵母来源的 VLPs 高 2.7 倍和 2.4 倍。我们的结果表明,表达系统的选择会严重影响 HPV16 L1 VLPs 的颗粒大小和免疫原性。

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