免疫原性
病毒学
人乳头瘤病毒疫苗
二价(发动机)
大肠杆菌
生物
人口
人乳头瘤病毒疫苗
免疫系统
医学
化学
宫颈癌
基因
遗传学
加德西
HPV感染
癌症
金属
有机化学
环境卫生
作者
Ying Gu,Minxi Wei,Daning Wang,Zhihai Li,Minghui Xie,Huirong Pan,Ting Wu,Jun Zhang,Shaowei Li,Ningshao Xia
出处
期刊:Vaccine
[Elsevier]
日期:2017-08-01
卷期号:35 (35): 4637-4645
被引量:37
标识
DOI:10.1016/j.vaccine.2017.06.084
摘要
Human papillomavirus (HPV) types 16 and 18 account for approximately 70% of cervical cancer worldwide. Neutralizing HPV prophylactic vaccines offer significant benefit, as they block HPV infection and prevent subsequent disease. However, the three licensed HPV vaccines that cover these two genotypes were produced in eukaryotic cells, which is expensive, particularly for low-income countries where HPV is highest. Here, we report a new HPV16 and -18 bivalent candidate vaccine produced from Escherichia coli. We used two strategies of N-terminal truncation of HPV L1 proteins and soluble non-fusion expression to generate HPV16 and HPV18 L1-only virus-like particles (VLPs) in a scalable process. Through comprehensive characterization of the bivalent candidate vaccine, we confirm lot consistency in a pilot scale-up of 30 L, 100 L and 500 L. Using cryo-EM 3D reconstruction, we found that HPV16 and -18 VLPs present in a T = 7 icosahedral arrangement, similar in shape and size to that of the native virions. This HPV16/18 bivalent vaccine shares comparable immunogenicity with the licensed vaccines. Overall, we show that the production of a HPV16/18 bivalent vaccine from an E. coli expression system is robust and scalable, with potentially good accessibility worldwide as a population-based immunization strategy.
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