title: Coadministration of a Plasmid Encoding HIV-1 Gag Enhances the Efficacy of Cancer DNA Vaccines.
abstract: DNA vaccination holds great promise for the prevention and treatment of cancer and infectious diseases. However, the clinical ability of DNA vaccines is still controversial due to the limited immune response initially observed in humans. We hypothesized that electroporation of a plasmid encoding the HIV-1 Gag viral capsid protein would enhance cancer DNA vaccine potency. DNA electroporation used to deliver plasmids in vivo, induced type I interferons, thereby supporting the activation of innate immunity. The coadministration of ovalbumin (OVA) and HIV-1 Gag encoding plasmids modulated the adaptive immune response. This strategy favored antigen-specific Th1 immunity, delayed B16F10-OVA tumor growth and improved mouse survival in both prophylactic and therapeutic vaccination approaches. Similarly, a prophylactic DNA immunization against the melanoma-associated antigen gp100 was enhanced by the codelivery of the HIV-1 Gag plasmid. The adjuvant effect was not driven by the formation of HIV-1 Gag virus-like particles. This work highlights the ability of both electroporation and the HIV-1 Gag plasmid to stimulate innate immunity for enhancing cancer DNA vaccine immunogenicity and demonstrates interesting tracks for the design of new translational genetic adjuvants to overcome the current limitations of DNA vaccines in humans.
authors.affiliation: Advanced Drug Delivery and Biomaterials, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Laure
authors.initials: L
authors.lastname: Lambricht
authors.affiliation: Advanced Drug Delivery and Biomaterials, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Kevin
authors.initials: K
authors.lastname: Vanvarenberg
authors.affiliation: Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
authors.forename: Ans
authors.initials: A
authors.lastname: De Beuckelaer
authors.affiliation: Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.|VIB Medical Biotechnology Center, Ghent University, Ghent, Belgium.
authors.forename: Lien
authors.initials: L
authors.lastname: Van Hoecke
authors.affiliation: Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Grooten
authors.affiliation: Advanced Drug Delivery and Biomaterials, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Bernard
authors.initials: B
authors.lastname: Ucakar
authors.affiliation: Bio and Soft Matter, Université catholique de Louvain, Louvain-La-Neuve, Belgium.
authors.forename: Pascale
authors.initials: P
authors.lastname: Lipnik
authors.affiliation: Laboratory of Gene Therapy, Ghent University, Ghent, Belgium.|Cancer Research Institute Ghent, Ghent, Belgium.
authors.forename: Niek N
authors.initials: NN
authors.lastname: Sanders
authors.affiliation: Institute for Laboratory Animal Science, Hannover Medical School, Hannover, Germany.|Institute for Experimental Infection Research, Centre for Experimental and Clinical Infection Research, TWINCORE, Hannover, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Lienenklaus
authors.affiliation: Advanced Drug Delivery and Biomaterials, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Véronique
authors.initials: V
authors.lastname: Préat
authors.affiliation: Advanced Drug Delivery and Biomaterials, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Vandermeulen
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000235:genetics* / Q000276:immunology*; D002460:Cell Line; D049109:Cell Proliferation; D004195:Disease Models, Animal; D006801:Humans; D007370:Interferon Type I / Q000096:biosynthesis; D008546:Melanoma, Experimental / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D051379:Mice; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics*; D016016:Proportional Hazards Models; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D014162:Transfection; D016896:Treatment Outcome; D047368:Tumor Burden; D019444:Vaccines, DNA / Q000235:genetics* / Q000276:immunology*; D058425:Vaccines, Virus-Like Particle / Q000235:genetics / Q000276:immunology / Q000648:ultrastructure; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics* / Q000276:immunology*
chemical_list: D019496:Cancer Vaccines; D007370:Interferon Type I; D019444:Vaccines, DNA; D058425:Vaccines, Virus-Like Particle; D054301:gag Gene Products, Human Immunodeficiency Virus