Efficient expression of enterovirus 71 based on virus-like particles vaccine.

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  • Additional Information
    • Source:
      Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
    • Publication Information:
      Original Publication: San Francisco, CA : Public Library of Science
    • Subject Terms:
      Antibodies, Neutralizing/*metabolism ; Antibodies, Viral/*metabolism ; Enterovirus A, Human/*genetics ; Vaccines, Virus-Like Particle/*genetics; Animals ; Baculoviridae ; Chlorocebus aethiops ; Enterovirus A, Human/immunology ; Female ; Genetic Engineering ; Mice ; Mice, Inbred BALB C ; Sf9 Cells ; Vaccination ; Vaccines, Virus-Like Particle/immunology ; Vero Cells
    • Abstract:
      Enterovirus (EV) 71 is the main pathogen associated with hand-foot-mouth disease (HFMD) and can lead to the disease with severe mortality in children. Since 2009, in the Republic of Korea, an outbreak of EV71 C4a infection with neurologic involvement emerged, where in HFMD involvement was identified and central nervous system complications were reported. In this study, EV71 C4a virus-like particles (VLPs) produced by recombinant technology were generated in a baculovirus expression system. To improve the production yield, EV71 VLP was constructed using the dual promoter system baculovirus P1 and 3CD (baculo-P1-3CD), which harbored both the structural protein-encoding P1 region under the control of the polyhedron promoter and the 3CD protease gene under the regulation of the CMV-IE, lef3, gp41, or chitinase promoters to augment the level of gene transcription. Efficient VLP expression was demonstrated through optimization of incubation time and insect cell type. In addition, to evaluate the potential of VLP as a vaccine candidate, we tested the neutralizing antibodies and total anti-EV71 IgG from the purified EV71 C4a VLP serum. The recombinant EV71 VLP exhibited the morphology of self-assembled VLP, as determined by electron microscopy. Use of baculo-P1-3CD-gp41 led to a high yield (11.3mg/L < 40kDa) of VLPs in High-FiveTM cells at 3 days post-infection. Furthermore, the potential of VLP as a vaccine was evaluated through the neutralizing ability elicited by the purified EV71 VLP after immunization of BALB/c mice, which was shown to induce potent and long-lasting humoral immune responses as evidenced by the cross-neutralization titer. Our results could be used to expedite the developmental process for vaccines under clinical trials and to ensure manufacturing consistency for licensing requirements.
      Competing Interests: The authors have declared that no competing interests exist.
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    • Accession Number:
      0 (Antibodies, Neutralizing)
      0 (Antibodies, Viral)
      0 (Vaccines, Virus-Like Particle)
    • Publication Date:
      Date Created: 20190308 Date Completed: 20191121 Latest Revision: 20200309
    • Publication Date:
      20240829
    • Accession Number:
      PMC6405078
    • Accession Number:
      10.1371/journal.pone.0210477
    • Accession Number:
      30845175