期刊
ANTIVIRAL RESEARCH
卷 159, 期 -, 页码 113-121出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.antiviral.2018.09.014
关键词
Venezuelan equine encephalitis virus; DNA vaccine; Genetic adjuvant; IL-12; GM-CSF; Alphavirus
资金
- Joint Science & Technology Office for Chemical & Biological Defense (JSTO-CBD) [CB10204]
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 T(h)1-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-alpha beta in DNA vaccine immunogenicity, we tested vaccine plasmids encoding a potent stimulator of the IFN-alpha beta 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.
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