A virus-like particle vaccine confers protection against enterovirus D68 lethal challenge in mice

Vaccine. 2018 Jan 29;36(5):653-659. doi: 10.1016/j.vaccine.2017.12.057. Epub 2017 Dec 30.


Enterovirus D68 (EV-D68) is increasingly associated with severe acute respiratory infection and acute flaccid myelitis (AFM) in children around the world. However, neither vaccines nor therapeutic drugs are available for EV-D68. Here we report the development of a virus-like particle (VLP) based experimental EV-D68 vaccine. We found that EV-D68 VLPs could be successfully generated in insect cells infected with a recombinant baculovirus co-expressing the P1 precursor and 3CD protease of EV-D68. Biochemical and electron microscopic analyses revealed that EV-D68 VLPs were composed of VP0, VP1, and VP3 capsid proteins derived from precursor P1 and were visualized as spherical particles of ∼30 nm in diameter. Immunization of mice with EV-D68 VLPs resulted in the production of serum antibodies that displayed potent serotype-specific neutralizing activities against EV-D68 virus in vitro. Passive transfer of anti-VLP sera completely protected neonatal recipient mice from lethal EV-D68 infection. Moreover, maternal immunization with these VLPs provided full protection against lethal EV-D68 challenge in suckling mice. Together, these results demonstrate that the recombinant EV-D68 VLP is a promising vaccine candidate against EV-D68 infection.

Keywords: Enterovirus D68; Vaccine; Virus-like particle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology
  • Capsid Proteins / genetics
  • Capsid Proteins / immunology
  • Enterovirus D, Human / immunology*
  • Enterovirus D, Human / ultrastructure
  • Enterovirus Infections / immunology*
  • Enterovirus Infections / prevention & control*
  • Gene Expression
  • Humans
  • Immunization
  • Immunogenicity, Vaccine
  • Mice
  • Neutralization Tests
  • Recombinant Proteins / immunology
  • Vaccines, Virus-Like Particle / administration & dosage
  • Vaccines, Virus-Like Particle / immunology*
  • Vaccines, Virus-Like Particle / ultrastructure


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Capsid Proteins
  • Recombinant Proteins
  • Vaccines, Virus-Like Particle