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

Details

Serval ID
serval:BIB_717715995FEF
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Electroporation of a nanoparticle-associated DNA vaccine induces higher inflammation and immunity compared to its delivery with microneedle patches in pigs.
Journal
Journal of controlled release
Author(s)
Bernelin-Cottet C., Urien C., McCaffrey J., Collins D., Donadei A., McDaid D., Jakob V., Barnier-Quer C., Collin N., Bouguyon E., Bordet E., Barc C., Boulesteix O., Leplat J.J., Blanc F., Contreras V., Bertho N., Moore A.C., Schwartz-Cornil I.
ISSN
1873-4995 (Electronic)
ISSN-L
0168-3659
Publication state
Published
Issued date
29/06/2019
Peer-reviewed
Oui
Volume
308
Pages
14-28
Language
english
Notes
Publication types: Journal Article
Abstract
DNA 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 MHC2 <sup>pos</sup> CD172A <sup>pos</sup> 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 MHC2 <sup>pos</sup> CD172A <sup>pos</sup> CD163 <sup>int</sup> and CD163 <sup>neg</sup> 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.
Keywords
DNA vaccines, Dissolvable microneedle, Electroporation, PLGA nanoparticles, Pig model, Skin
Pubmed
Create date
18/07/2019 16:15
Last modification date
21/08/2019 5:36
Usage data