Characterization of human enterovirus71 virus-like particles used for vaccine antigens

PLoS One. 2017 Jul 21;12(7):e0181182. doi: 10.1371/journal.pone.0181182. eCollection 2017.

Abstract

Human enterovirus 71 (EV71) is a major causative pathogen of hand, foot and mouth disease (HFMD) and has caused outbreaks with significant mortality among young children in the Asia-Pacific region in recent years. Towards developing a vaccine for this disease, we have expressed and purified EV71 virus-like particles (VLPs), which resemble the authentic virus in appearance, capsid structure and protein sequence, from insect cells (Sf9) using a multistep chromatography process. We demonstrated intracellular localization of the VLPs in host cells by in situ immunogold detection, electron microscopy and immunofluorescence. Characteristics of these EV71 VLPs were studied using a variety of immunological and physicochemical techniques, which aimed to reveal that the purified EV71 VLPs have good morphology and structure consistent with natural EV71 empty capsids. Results of the amino acid analysis, SDS-PAGE, Western blotting and high-performance liquid chromatography confirmed the high purity of the EV71 VLPs. However the sedimentation coefficient of the VLPs showed that they were smaller than that of secreted EV71 VLPs purified by discontinuous cesium chloride density gradients, they were similar to the empty capsids of natural EV71 virions reported previously. Combined with the previous study that EV71 VLPs purified by a multistep chromatography process were able to elicit strong humoral immune responses in mice, our results further supported the conclusion that our EV71 VLPs had well-preserved molecular and structural characteristics. The EV71 VLPs produced from the baculovirus expression system and purified by a multistep chromatography process displayed key structural and immunological features, which would contribute to their efficacy as a HFMD vaccine.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Blotting, Western
  • Chromatography, High Pressure Liquid
  • Dynamic Light Scattering
  • Electrophoresis, Polyacrylamide Gel
  • Enterovirus A, Human / genetics
  • Enterovirus A, Human / immunology*
  • Immunohistochemistry
  • Mass Spectrometry
  • Microscopy, Atomic Force
  • Microscopy, Confocal
  • Microscopy, Electron, Transmission
  • Sf9 Cells
  • Vaccines, Virus-Like Particle / chemistry*
  • Vaccines, Virus-Like Particle / genetics
  • Vaccines, Virus-Like Particle / immunology*
  • Vaccines, Virus-Like Particle / ultrastructure
  • Viral Vaccines / chemistry*
  • Viral Vaccines / immunology*

Substances

  • Vaccines, Virus-Like Particle
  • Viral Vaccines

Grants and funding

This study was funded by Jilin Province Science and Technology Development Program (No.20130204013YY, No.20130521001JH, No.20160209016YY) and the National Science and Technology Major Project of the Ministry of Science and Technology of China (No.2012ZX10001009-002). The authors (D W and Y C and Y M) employed by a commercial company, Changchun BCHT Biotechnology Company, are responsible for preparation of the EV71 VLPs, and the author (L B) is responsible for Sf9 cell culture.