2.50
Hdl Handle:
http://hdl.handle.net/10033/621303
Title:
Coadministration of a Plasmid Encoding HIV-1 Gag Enhances the Efficacy of Cancer DNA Vaccines.
Authors:
Lambricht, Laure; Vanvarenberg, Kevin; De Beuckelaer, Ans; Van Hoecke, Lien; Grooten, Johan; Ucakar, Bernard; Lipnik, Pascale; Sanders, Niek N; Lienenklaus, Stefan; Préat, Véronique; Vandermeulen, Gaëlle
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.
Affiliation:
TWINCORE, Zentrum für experimentelle und klinischeInfektionsforschung GmbH, Feodor-Lynen-Str. 7, 30625 Hannover, Germany.
Citation:
Coadministration of a Plasmid Encoding HIV-1 Gag Enhances the Efficacy of Cancer DNA Vaccines. 2016, 24 (9):1686-96 Mol. Ther.
Journal:
Molecular therapy : the journal of the American Society of Gene Therapy
Issue Date:
2016
URI:
http://hdl.handle.net/10033/621303
DOI:
10.1038/mt.2016.122
PubMed ID:
27434590
Type:
Article
Language:
en
ISSN:
1525-0024
Appears in Collections:
publications of the department of experimental infection research ([TC] EXPI)

Full metadata record

DC FieldValue Language
dc.contributor.authorLambricht, Laureen
dc.contributor.authorVanvarenberg, Kevinen
dc.contributor.authorDe Beuckelaer, Ansen
dc.contributor.authorVan Hoecke, Lienen
dc.contributor.authorGrooten, Johanen
dc.contributor.authorUcakar, Bernarden
dc.contributor.authorLipnik, Pascaleen
dc.contributor.authorSanders, Niek Nen
dc.contributor.authorLienenklaus, Stefanen
dc.contributor.authorPréat, Véroniqueen
dc.contributor.authorVandermeulen, Gaëlleen
dc.date.accessioned2018-03-02T15:43:27Z-
dc.date.available2018-03-02T15:43:27Z-
dc.date.issued2016-
dc.identifier.citationCoadministration of a Plasmid Encoding HIV-1 Gag Enhances the Efficacy of Cancer DNA Vaccines. 2016, 24 (9):1686-96 Mol. Ther.en
dc.identifier.issn1525-0024-
dc.identifier.pmid27434590-
dc.identifier.doi10.1038/mt.2016.122-
dc.identifier.urihttp://hdl.handle.net/10033/621303-
dc.description.abstractDNA 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.en
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subject.meshAnimalsen
dc.subject.meshCancer Vaccinesen
dc.subject.meshCell Lineen
dc.subject.meshCell Proliferationen
dc.subject.meshDisease Models, Animalen
dc.subject.meshHumansen
dc.subject.meshInterferon Type Ien
dc.subject.meshMelanoma, Experimentalen
dc.subject.meshMiceen
dc.subject.meshPlasmidsen
dc.subject.meshProportional Hazards Modelsen
dc.subject.meshTh1 Cellsen
dc.subject.meshTransfectionen
dc.subject.meshTreatment Outcomeen
dc.subject.meshTumor Burdenen
dc.subject.meshVaccines, DNAen
dc.subject.meshVaccines, Virus-Like Particleen
dc.subject.meshgag Gene Products, Human Immunodeficiency Virusen
dc.titleCoadministration of a Plasmid Encoding HIV-1 Gag Enhances the Efficacy of Cancer DNA Vaccines.en
dc.typeArticleen
dc.contributor.departmentTWINCORE, Zentrum für experimentelle und klinischeInfektionsforschung GmbH, Feodor-Lynen-Str. 7, 30625 Hannover, Germany.en
dc.identifier.journalMolecular therapy : the journal of the American Society of Gene Therapyen

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