Nanoplasmid Vectors Co-expressing Innate Immune Agonists Enhance DNA Vaccines for Venezuelan Equine Encephalitis Virus and Ebola Virus

Suschak, John J.; Dupuy, Lesley C.; Shoemaker, Charles J.; Six, Carolyn; Kwilas, Steven A.; Spik, Kristin W.; Williams, James A.; Schmaljohn, Connie S.

doi:10.1016/j.omtm.2020.04.009

Title: Nanoplasmid Vectors Co-expressing Innate Immune Agonists Enhance DNA Vaccines for Venezuelan Equine Encephalitis Virus and Ebola Virus

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Abstract

DNA vaccines expressing codon-optimized Venezuelan equine encephalitis virus (VEEV) and Ebola virus (EBOV) glycoprotein genes provide protective immunity to mice and nonhuman primates when delivered by intramuscular (IM) electroporation (EP). To achieve equivalent protective efficacy in the absence of EP, we evaluated VEEV and EBOV DNA vaccines constructed using minimalized Nanoplasmid expression vectors that are smaller than conventional plasmids used for DNA vaccination. These vectors may also be designed to co-express type I interferon inducing innate immune agonist genes that have an adjuvant effect. Nanoplasmid vaccinated mice had increased antibody responses as compared to those receiving our conventional pWRG7077-based vaccines when delivered by IM injection, and these responses were further enhanced by the inclusion of the innate immune agonist genes. The Nanoplasmid VEEV DNA vaccines also significantly increased protection against aerosol VEEV challenge as compared to the pWRG7077 VEEV DNA vaccine. Although all mice receiving the pWRG7077 and Nanoplasmid EBOV DNA vaccines at the dose tested survived EBOV challenge, only mice receiving the Nanoplasmid EBOV DNA vaccine that co-expresses the innate immune agonist genes failed to lose weight after challenge. Our results suggest that Nanoplasmid vectors can improve the immunogenicity and protective efficacy of alphavirus and filovirus DNA vaccines.

Authors:: Suschak, John J.; Dupuy, Lesley C.; Shoemaker, Charles J.; Six, Carolyn; Kwilas, Steven A.; Spik, Kristin W.; Williams, James A.; Schmaljohn, Connie S.

Publication Date:: Mon Jun 01 00:00:00 EDT 2020

Research Org.:: Oak Ridge Inst. for Science and Education (ORISE), Oak Ridge, TN (United States)

Sponsoring Org.:: USDOE Office of Science (SC)

OSTI Identifier:: 1616216

Alternate Identifier(s):: OSTI ID: 1816514

Grant/Contract Number:: SC0014664

Resource Type:: Published Article

Journal Name:: Molecular Therapy - Methods & Clinical Development

Additional Journal Information:: Journal Name: Molecular Therapy - Methods & Clinical Development Journal Volume: 17 Journal Issue: C; Journal ID: ISSN 2329-0501

Publisher:: Elsevier

Country of Publication:: Country unknown/Code not available

Language:: English

Subject:: 59 BASIC BIOLOGICAL SCIENCES; DNA vaccine; nanoplasmid; genetic adjuvant; innate immune agonist; RIG-I; CpG; immunostimulatory RNA; Ebola virus; Venezuelan equine encephalitis virus

Citation Formats


                    Suschak, John J., Dupuy, Lesley C., Shoemaker, Charles J., Six, Carolyn, Kwilas, Steven A., Spik, Kristin W., Williams, James A., and Schmaljohn, Connie S. Nanoplasmid Vectors Co-expressing Innate Immune Agonists Enhance DNA Vaccines for Venezuelan Equine Encephalitis Virus and Ebola Virus.  Country unknown/Code not available: N. p., 2020. 
Web.  doi:10.1016/j.omtm.2020.04.009.

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                    Suschak, John J., Dupuy, Lesley C., Shoemaker, Charles J., Six, Carolyn, Kwilas, Steven A., Spik, Kristin W., Williams, James A., & Schmaljohn, Connie S. Nanoplasmid Vectors Co-expressing Innate Immune Agonists Enhance DNA Vaccines for Venezuelan Equine Encephalitis Virus and Ebola Virus.  Country unknown/Code not available.  https://doi.org/10.1016/j.omtm.2020.04.009

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                    Suschak, John J., Dupuy, Lesley C., Shoemaker, Charles J., Six, Carolyn, Kwilas, Steven A., Spik, Kristin W., Williams, James A., and Schmaljohn, Connie S. Mon .  
"Nanoplasmid Vectors Co-expressing Innate Immune Agonists Enhance DNA Vaccines for Venezuelan Equine Encephalitis Virus and Ebola Virus".  Country unknown/Code not available.  https://doi.org/10.1016/j.omtm.2020.04.009.

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@article{osti_1616216,

  title        = {Nanoplasmid Vectors Co-expressing Innate Immune Agonists Enhance DNA Vaccines for Venezuelan Equine Encephalitis Virus and Ebola Virus},

  author       = {Suschak, John J. and Dupuy, Lesley C. and Shoemaker, Charles J. and Six, Carolyn and Kwilas, Steven A. and Spik, Kristin W. and Williams, James A. and Schmaljohn, Connie S.},

  abstractNote = {DNA vaccines expressing codon-optimized Venezuelan equine encephalitis virus (VEEV) and Ebola virus (EBOV) glycoprotein genes provide protective immunity to mice and nonhuman primates when delivered by intramuscular (IM) electroporation (EP). To achieve equivalent protective efficacy in the absence of EP, we evaluated VEEV and EBOV DNA vaccines constructed using minimalized Nanoplasmid expression vectors that are smaller than conventional plasmids used for DNA vaccination. These vectors may also be designed to co-express type I interferon inducing innate immune agonist genes that have an adjuvant effect. Nanoplasmid vaccinated mice had increased antibody responses as compared to those receiving our conventional pWRG7077-based vaccines when delivered by IM injection, and these responses were further enhanced by the inclusion of the innate immune agonist genes. The Nanoplasmid VEEV DNA vaccines also significantly increased protection against aerosol VEEV challenge as compared to the pWRG7077 VEEV DNA vaccine. Although all mice receiving the pWRG7077 and Nanoplasmid EBOV DNA vaccines at the dose tested survived EBOV challenge, only mice receiving the Nanoplasmid EBOV DNA vaccine that co-expresses the innate immune agonist genes failed to lose weight after challenge. Our results suggest that Nanoplasmid vectors can improve the immunogenicity and protective efficacy of alphavirus and filovirus DNA vaccines.},

  doi          = {10.1016/j.omtm.2020.04.009},

  journal      = {Molecular Therapy - Methods & Clinical Development},

  number       = C,

  volume       = 17,

  place        = {Country unknown/Code not available},

  year         = {Mon Jun 01 00:00:00 EDT 2020},

  month        = {Mon Jun 01 00:00:00 EDT 2020}

}

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