Electroporation of a nanoparticle-associated DNA vaccine induces higher inflammation and immunity compared to its delivery with microneedle patches in pigs

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dc.contributor.authorBernelin-Cottet, Cindy
dc.contributor.authorUrien, Céline
dc.contributor.authorMcCaffrey, Joanne
dc.contributor.authorCollins, Damien
dc.contributor.authorDonadei, Agnese
dc.contributor.authorMcDaid, Dennis
dc.contributor.authorJakob, Virginie
dc.contributor.authorBarnier-Quer, Christophe
dc.contributor.authorCollin, Nicolas
dc.contributor.authorBouguyon, Edwige
dc.contributor.authorBordet, Elise
dc.contributor.authorBarc, Céline
dc.contributor.authorBoulesteix, Olivier
dc.contributor.authorLeplat, Jean-Jacques
dc.contributor.authorBlanc, Fany
dc.contributor.authorContreras, Vanessa
dc.contributor.authorBertho, Nicolas
dc.contributor.authorMoore, Anne C.
dc.contributor.authorSchwartz-Cornil, Isabelle
dc.contributor.funderHorizon 2020en
dc.contributor.funderInstitut National de la Recherche Agronomiqueen
dc.date.accessioned2019-10-30T06:45:30Z
dc.date.available2019-10-30T06:45:30Z
dc.date.issued2018-08-28
dc.description.abstractDNA vaccination is an attractive technology, based on its well-established manufacturing process, safety profile, adaptability to rapidly combat pandemic pathogens, and stability at ambient temperature; however an optimal delivery method of DNA remains to be determined. As pigs are a relevant model for humans, we comparatively evaluated the efficiency of vaccine DNA delivery in vivo to pigs using dissolvable microneedle patches, intradermal inoculation with needle (ID), surface electroporation (EP), with DNA associated or not to cationic poly-lactic-co-glycolic acid nanoparticles (NPs). We used a luciferase encoding plasmid (pLuc) as a reporter and vaccine plasmids encoding antigens from the Porcine Reproductive and Respiratory Syndrome Virus (PRRSV), a clinically-significant swine arterivirus. Patches were successful at inducing luciferase expression in skin although at lower level than EP. EP induced the cutaneaous recruitment of granulocytes, of MHC2posCD172Apos myeloid cells and type 1 conventional dendritic cells, in association with local production of IL-1β, IL-8 and IL-17; these local responses were more limited with ID and undetectable with patches. The addition of NP to EP especially promoted the recruitment of the MHC2posCD172Apos CD163int and CD163neg myeloid subsets. Notably we obtained the strongest and broadest IFNγ T-cell response against a panel of PRRSV antigens with DNA + NPs delivered by EP, whereas patches and ID were ineffective. The anti-PRRSV IgG responses were the highest with EP administration independently of NPs, mild with ID, and undetectable with patches. These results contrast with the immunogenicity and efficacy previously induced in mice with patches. This study concludes that successful DNA vaccine administration in skin can be achieved in pigs with electroporation and patches, but only the former induces local inflammation, humoral and cellular immunity, with the highest potency when NPs were used. This finding shows the importance of evaluating the delivery and immunogenicity of DNA vaccines beyond the mouse model in a preclinical model relevant to human such as pig and reveals that EP with DNA combined to NP induces strong immunogenicity.en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationBernelin-Cottet, C., Urien, C., McCaffrey, J., Collins, D., Donadei, A., McDaid, D., Jakob, V., Barnier-Quer, C., Collin, N., Bouguyon, E. and Bordet, E., 2019. Electroporation of a nanoparticle-associated DNA vaccine induces higher inflammation and immunity compared to its delivery with microneedle patches in pigs. Journal of Controlled Release. 308, pp. 14-28. DOI:10.1016/j.jconrel.2019.06.041en
dc.identifier.doi10.1016/j.jconrel.2019.06.041en
dc.identifier.eissn1873-4995
dc.identifier.endpage28en
dc.identifier.issn0168-3659
dc.identifier.journaltitleJournal of Controlled Releaseen
dc.identifier.startpage14en
dc.identifier.urihttps://hdl.handle.net/10468/8925
dc.identifier.volume308en
dc.language.isoenen
dc.publisherElsevieren
dc.relation.projectinfo:eu-repo/grantAgreement/EC/H2020::RIA/633184/EU/Strengthening Animal Production and Health through the Immune Response/SAPHIRen
dc.relation.urihttps://www.sciencedirect.com/science/article/pii/S0168365919303840
dc.rights© 2019 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND licenseen
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectDNA vaccinesen
dc.subjectSkinen
dc.subjectPig modelen
dc.subjectDissolvable microneedleen
dc.subjectElectroporationen
dc.subjectPLGA nanoparticlesen
dc.titleElectroporation of a nanoparticle-associated DNA vaccine induces higher inflammation and immunity compared to its delivery with microneedle patches in pigsen
dc.typeArticle (peer-reviewed)en
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