The genetic adjuvant IL-12 enhances the protective efficacy of a DNA vaccine for Venezuelan equine encephalitis virus delivered by intramuscular injection in mice
| Autor: | Connie S. Schmaljohn, Lesley C. Dupuy, Carolyn Six, Kristin Spik, Steven A. Kwilas, Kenneth Bagley, John J. Suschak, Charles J. Shoemaker |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
medicine.medical_treatment Alphavirus Biology Antibodies Viral medicine.disease_cause Injections Intramuscular DNA vaccination Encephalitis Virus Venezuelan Equine Mice 03 medical and health sciences Immunogenicity Vaccine Immune system Adjuvants Immunologic Virology Vaccines DNA medicine Animals Pharmacology Mice Inbred BALB C Immunogenicity Electroporation Granulocyte-Macrophage Colony-Stimulating Factor Encephalomyelitis Venezuelan Equine Viral Vaccines biology.organism_classification Antibodies Neutralizing Interleukin-12 Vaccination 030104 developmental biology Venezuelan equine encephalitis virus Female Adjuvant |
| Zdroj: | Antiviral Research. 159:113-121 |
| ISSN: | 0166-3542 |
| DOI: | 10.1016/j.antiviral.2018.09.014 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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