doi: 10.1038/s41541-017-0006-8. eCollection 2017.
Escherichia coli- derived virus-like particles in vaccine development
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- PMID:29263864
- PMCID: PMC5627247
- DOI: 10.1038/s41541-017-0006-8
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Escherichia coli- derived virus-like particles in vaccine development
Xiaofen Huang et al. NPJ Vaccines..
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Abstract
Recombinant virus-like particle-based vaccines are composed of viral structural proteins and mimic authentic native viruses but are devoid of viral genetic materials. They are the active components in highly safe and effective vaccines for the prevention of infectious diseases. Several expression systems have been used for virus-like particle production, ranging fromEscherichia coli to mammalian cell lines. The prokaryotic expression system, especiallyEscherichia coli, is the preferred expression host for producing vaccines for global use. Hecolin, the first licensed virus-like particle vaccine derived fromEscherichia coli, has been demonstrated to possess good safety and high efficacy. In this review, we focus onEscherichia coli-derived virus-like particle based vaccines and vaccine candidates that are used for prevention (immunization against microbial pathogens) or disease treatment (directed against cancer or non-infectious diseases). The native-like spatial or higher-order structure is essential for the function of virus-like particles. Thus, the tool box for analyzing the key physicochemical, biochemical and functional attributes of purified virus-like particles will also be discussed. In summary, theEscherichia coli expression system has great potentials for producing a range of proteins with self-assembling properties to be used as vaccine antigens given the proper epitopes were preserved when compared to those in the native pathogens or disease-related target molecules.
Figures
The number of VLP-based vaccines or vaccine candidates that were approved and in clinical studies from 1986 to 2015. Total numbers of VLP vaccines or candidates derived from different expression systems (includingE. coli) are plotted on the left. The numbers of commercialized VLP vaccines or those being tested in clinical trials derived fromE. coli are plotted on the right.
Analytical toolbox for the characterization of VLPs. A series of modern techniques make up a “toolbox” that has been extensively used for structural and functional characterization of VLPs. Biochemical:SDS-PAGE sodium dodecyl sulphate polyacrylamide gel electrophoresis,MALDI-TOF MS matrix-assisted laser desorption/ionization time of flight mass spectrometry,LC-MS liquid chromatography–mass spectrometry,icIEF imaged capillary isoelectric focusing has been widely used for protein characterization, Biophysical: the morphology of VLPs can be observed by TEM, Cry-EM, and AFM.TEM transmission electron microscopy,Cry-EM cry electron microscopy,AFM atomic force microscopy, AF4-MALS, DLS, ES-DMA, and HPSEC generally are used for the measurement the size of particles.AF4-MALS asymmetric flow field-flow fractionation coupled with multiple-angle light scattering,,DLS dynamic light scattering,ES-DMA electrospray differential mobility analysis,HPSEC high performance size exclusion chromatography,AUC analytical ultracentrifugation,CD Circular dichroism,UV ultraviolet spectroscopy,DSC differential scanning calorimetry, mAb or pAb-based assays are used to measure the concentration of functional epitopes in the vaccine samples. Epitope-mapping: comparable of epitope overlap of VLPs in different vaccine samples by mAbs;SPR surface plasmon resonance,IVRP in vitro relative potency,KD equilibrium dissociation constant,IC50 half maximal inhibitory concentration,ELISA enzyme-linked immunosorbent assay, The mini-VLP in the figure is the structure mode of HPV59, which was adapted from Structure, Li et al.
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