|Entry||Database: EMDB / ID: 6795|
|Title||CryoEM structure of HPV16 L1-only VLP|
|Method||single particle reconstruction / cryo EM / 30 Å resolution|
|Authors||Li ZH / Yan XD / Zheng QB / Gu Y / Li SW|
|Citation||Journal: Vaccine / Year: 2017|
Title: Characterization of an Escherichia coli-derived human papillomavirus type 16 and 18 bivalent vaccine.
Authors: Ying Gu / Minxi Wei / Daning Wang / Zhihai Li / Minghui Xie / Huirong Pan / Ting Wu / Jun Zhang / Shaowei Li / Ningshao Xia
Abstract: 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 ...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 30L, 100L and 500L. Using cryo-EM 3D reconstruction, we found that HPV16 and -18VLPs 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.
|Date||Deposition: Jul 15, 2017 / Header (metadata) release: Sep 6, 2017 / Map release: Sep 6, 2017 / Last update: Sep 6, 2017|
|Structure viewer||EM map: |
Downloads & links
|File||emd_6795.map.gz (map file in CCP4 format, 23329 KB)|
|Projections & slices|
Images are generated by Spider.
|Voxel size||X=Y=Z: 4.44 Å|
CCP4 map header:
-Entire Alphapapillomavirus 9
|Entire||Name: Alphapapillomavirus 9 / Number of components: 1|
-Component #1: virus, Alphapapillomavirus 9
|Virus||Name: Alphapapillomavirus 9 / Class: VIRUS-LIKE PARTICLE / Empty: Yes / Enveloped: No / Isolate: OTHER|
|Species||Species: Alphapapillomavirus 9|
|Source (engineered)||Expression System: Escherichia coli (E. coli)|
|Specimen||Specimen state: particle / Method: cryo EM|
|Sample solution||pH: 7.3|
|Vitrification||Cryogen name: ETHANE|
-Electron microscopy imaging
Model: Tecnai F30 / Image courtesy: FEI Company
|Imaging||Microscope: FEI TECNAI F30|
|Electron gun||Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Electron dose: 25 e/Å2 / Illumination mode: OTHER|
|Lens||Imaging mode: BRIGHT FIELD|
|Specimen Holder||Model: OTHER|
|Camera||Detector: FEI FALCON I (4k x 4k)|
|Processing||Method: single particle reconstruction / Number of projections: 400|
|3D reconstruction||Resolution: 30 Å / Resolution method: FSC 0.5 CUT-OFF|
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