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The genetic adjuvant IL-12 enhances the protective efficacy of a DNA vaccine for Venezuelan equine encephalitis virus delivered by intramuscular injection in mice.
Suschak, John J; Bagley, Kenneth; Six, Carolyn; Shoemaker, Charles J; Kwilas, Steven; Spik, Kristin W; Dupuy, Lesley C; Schmaljohn, Connie S.
Afiliación
  • Suschak JJ; U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA.
  • Bagley K; Profectus BioSciences Inc, Baltimore, MD 21224, USA.
  • Six C; U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA.
  • Shoemaker CJ; U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA.
  • Kwilas S; U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA.
  • Spik KW; U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA.
  • Dupuy LC; U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA.
  • Schmaljohn CS; U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA. Electronic address: connie.s.schmaljohn.civ@mail.mil.
Antiviral Res ; 159: 113-121, 2018 11.
Article en En | MEDLINE | ID: mdl-30268913
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-αß in DNA vaccine immunogenicity, we tested vaccine plasmids encoding a potent stimulator of the IFN-αß 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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vacunas Virales / Adyuvantes Inmunológicos / Interleucina-12 / Vacunas de ADN / Encefalomielitis Equina Venezolana / Inmunogenicidad Vacunal Límite: Animals País/Región como asunto: America do sul / Venezuela Idioma: En Revista: Antiviral Res Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Países Bajos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vacunas Virales / Adyuvantes Inmunológicos / Interleucina-12 / Vacunas de ADN / Encefalomielitis Equina Venezolana / Inmunogenicidad Vacunal Límite: Animals País/Región como asunto: America do sul / Venezuela Idioma: En Revista: Antiviral Res Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Países Bajos