The genetic adjuvant IL-12 enhances the protective efficacy of a DNA vaccine for Venezuelan equine encephalitis virus delivered by intramuscular injection in mice

Antiviral Res. 2018 Nov:159:113-121. doi: 10.1016/j.antiviral.2018.09.014. Epub 2018 Sep 27.

Abstract

We have previously shown that DNA vaccines expressing codon-optimized alphavirus envelope glycoprotein genes protect both mice and non-human primates from viral challenge when delivered by intramuscular electroporation (IM-EP). To determine if we could achieve equivalent immunogenicity and protective efficacy in the absence of electroporation, we co-delivered our Venezuelan equine encephalitis virus (VEEV) DNA vaccine with DNA plasmids expressing genetic adjuvants designed to augment immune responses. We tested the Th1-inducing cytokine IL-12 as well as the granulocyte growth factor GM-CSF, both of which have demonstrated significant adjuvant effect when included in clinical DNA vaccine formulations. Additionally, as multiple reports have described the necessity of IFN-αβ in DNA vaccine immunogenicity, we tested vaccine plasmids encoding a potent stimulator of the IFN-αβ pathway. Our data suggest that IM vaccination of mice with plasmid DNA encoding genetic adjuvants enhances VEEV vaccine immunogenicity, resulting in improved T cell responses, as well as skewing of the anti-VEEV IgG antibody isotype. Additionally, IM vaccination of VEEV DNA vaccine and IL-12 provided complete protection against aerosol VEEV challenge. Overall, our data suggest that co-delivery of genetic adjuvants with alphavirus DNA vaccines using IM delivery can influence the type of immune response obtained and provide comparable protective immunity to that achieved by IM-EP delivery of the vaccine without adjuvants.

Keywords: Alphavirus; DNA vaccine; GM-CSF; Genetic adjuvant; IL-12; Venezuelan equine encephalitis virus.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adjuvants, Immunologic*
  • Animals
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology
  • Encephalitis Virus, Venezuelan Equine
  • Encephalomyelitis, Venezuelan Equine / immunology
  • Encephalomyelitis, Venezuelan Equine / prevention & control*
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology
  • Immunogenicity, Vaccine*
  • Injections, Intramuscular
  • Interleukin-12 / genetics
  • Interleukin-12 / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Vaccines, DNA / immunology*
  • Viral Vaccines / immunology*

Substances

  • Adjuvants, Immunologic
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Vaccines, DNA
  • Viral Vaccines
  • Interleukin-12
  • Granulocyte-Macrophage Colony-Stimulating Factor