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Skin Dendritic Cell Targeting via Microneedle Arrays Laden with Antigen Encapsulated Poly-D-L-Lactide-co-Glycolide Nanoparticles Induces Efficient Ant

tetano

Editor, Senior Moderator
ACS Nano. 2013 Feb 2. [Epub ahead of print]
Skin Dendritic Cell Targeting via Microneedle Arrays Laden with Antigen Encapsulated Poly-D-L-Lactide-co-Glycolide Nanoparticles Induces Efficient Anti-Tumour and Anti-Viral Immune Responses.
Zaric M, Lyubomska O, Touzelet O, Poux C, Al-Zahrani S, Fay F, Wallace L, Terhorst D, Malissen B, Henri S, Power UF, Scott CJ, Donnelly RF, Kissenpfennig A.
Abstract

The efficacious delivery of antigens to antigen-presenting cells (APCs), in particular to dendritic cells (DCs), and their subsequent activation remains a significant challenge in the development of effective vaccines. This study highlights the potential of dissolving microneedle arrays laden with nano-encapsulated antigen to increase vaccine immunogenicity by targeting antigen specifically to contiguous DCs networks within the skin. Following in situ uptake, skin resident DCs were able to deliver antigen encapsulated poly-D-L-lactide-co-glycolide (PGLA) nanoparticles to cutaneous draining lymph nodes where they subsequently induced significant expansion of antigen-specific T cells. Moreover, we show that antigen encapsulated nanoparticle vaccination via microneedles generated robust antigen specific cellular immune responses in mice. This approach provided complete protection in vivo against both the development of antigen-expressing B16 melanoma tumours and a murine model of para-influenza, through the activation of antigen-specific cytotoxic CD8+ T cells that resulted in efficient clearance of tumours and virus, respectively. In addition, we show promising findings that nano-encapsulation facilitates antigen retention into skin layers and provides antigen stability in microneedles. Therefore, the use of biodegradable polymeric nanoparticles for selective targeting of antigen to skin DCs subsets through dissolvable MNs provides a promising technology for improved vaccination efficacy, compliance and coverage.

PMID:
23373658
[PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/pubmed/23373658
 
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