Electroporation enhances protective immune response of a DNA vaccine against Japanese encephalitis in mice and pigs

Vaccine. 2016 Nov 11;34(47):5751-5757. doi: 10.1016/j.vaccine.2016.10.001. Epub 2016 Oct 13.

Abstract

Japanese encephalitis virus (JEV) is a pathogenic cause of Japanese Encephalitis (JE), which is a zoonotic disease transmitted by mosquitoes and amplified by pigs. Infection of JEV may lead to severe neurological sequelae, even death in humans and reproductive disorders in pigs. Vaccination is the only way to control JEV infection in humans. For pigs play important role in the JEV transmission cycle, developing a new veterinary vaccine is considered as a useful strategy for cutting off the transmission route of JEV. We have previously reported that DNA vaccine pCAG-JME, expressing prM-E proteins of JEV, is effective in mice through intramuscular injection (IM). However, the poor immunogenicity, due to low expression of immunogen, is the major obstacle for the development of DNA vaccine in large animals. In the present study, therefore, we immunized mice and pigs with pCAG-JME intramuscularly accompanied with electroporation (EP) stimulation, the attractive gene delivery approach. As compared with IM, EP-mediated vaccination markedly increased the expression of immunogen in the injection site and induced a dose- and time-dependent immune response. 100% survival rate was observed in groups vaccinated with doses ranged from 10 to 100μg, indicating that 10μg of DNA with EP for individual was enough for inducing effective protection in mice. Surprisingly, survival rate and end-point titers of anti-JEV antibodies were higher in mice even at lower dose of DNA (5μg) than that in mice inoculated 100μg through IM. Notably, the prM-E antigens also induced high antibody response in pig, while the neutralizing antibody titer achieved 1:320. Our results suggested that EP-mediated DNA immunization might act as an effective strategy against JEV, at least in pig, and that EP has a potential application prospect in DNA vaccination.

Keywords: DNA vaccine; Electroporation; Japanese encephalitis virus; Mice; Swine.

MeSH terms

  • Animals
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood
  • Chlorocebus aethiops
  • Electroporation / methods*
  • Encephalitis Virus, Japanese / genetics
  • Encephalitis Virus, Japanese / immunology*
  • Encephalitis, Japanese / prevention & control*
  • Female
  • Gene Transfer Techniques
  • Humans
  • Immunity, Active
  • Immunogenicity, Vaccine*
  • Immunologic Factors / blood
  • Injections, Intramuscular
  • Japanese Encephalitis Vaccines / administration & dosage*
  • Japanese Encephalitis Vaccines / genetics
  • Japanese Encephalitis Vaccines / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Swine
  • Time Factors
  • Vaccination / veterinary
  • Vaccines, DNA / administration & dosage
  • Vaccines, DNA / genetics
  • Vaccines, DNA / immunology
  • Vero Cells
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / immunology*
  • Viral Envelope Proteins / metabolism

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Immunologic Factors
  • Japanese Encephalitis Vaccines
  • Vaccines, DNA
  • Viral Envelope Proteins