Skin dendritic cell targeting via microneedle arrays laden with antigen-encapsulated poly-D,L-lactide-co-glycolide nanoparticles induces efficient antitumor and antiviral immune responses.
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 (MN) arrays laden with nanoencapsulated antigen to increase vaccine immunogenicity by targeting antigen specifically to contiguous DC 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 tumors and a murine model of para-influenza, through the activation of antigen-specific cytotoxic CD8(+) T cells that resulted in efficient clearance of tumors and virus, respectively. In addition, we show promising findings that nanoencapsulation 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 DC subsets through dissolvable MNs provides a promising technology for improved vaccination efficacy, compliance, and coverage.
The Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, University Road, Belfast BT9 7AE, United Kingdom.
Marija
M
Zaric
Oksana
O
Lyubomska
Olivier
O
Touzelet
Candice
C
Poux
Sharifah
S
Al-Zahrani
Francois
F
Fay
Leah
L
Wallace
Dorothea
D
Terhorst
Bernard
B
Malissen
Sandrine
S
Henri
Ultan F
UF
Power
Christopher J
CJ
Scott
Ryan F
RF
Donnelly
Adrien
A
Kissenpfennig
D056704:Adaptive Immunity; D000818:Animals; D000941:Antigens / Q000008:administration & dosage*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry; D003713:Dendritic Cells / Q000276:immunology*; D016503:Drug Delivery Systems; D005260:Female; D007271:Injections, Intradermal; D008297:Male; D008546:Melanoma, Experimental / Q000276:immunology / Q000517:prevention & control; D051379:Mice; D008822:Mice, Transgenic; D053769:Nanocapsules / Q000008:administration & dosage* / Q000737:chemistry; D036103:Nanotechnology; D009339:Needles; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010253:Respirovirus Infections / Q000276:immunology / Q000517:prevention & control; D029082:Sendai virus / Q000276:immunology; D012867:Skin / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014612:Vaccines / Q000008:administration & dosage
D000941:Antigens; D023181:Antimicrobial Cationic Peptides; D053769:Nanocapsules; D014612:Vaccines; C045866:peptide-Gly-Leu-amide; D010047:Ovalbumin