title: Langerin negative dendritic cells promote potent CD8+ T-cell priming by skin delivery of live adenovirus vaccine microneedle arrays.
abstract: Stabilization of virus protein structure and nucleic acid integrity is challenging yet essential to preserve the transcriptional competence of live recombinant viral vaccine vectors in the absence of a cold chain. When coupled with needle-free skin delivery, such a platform would address an unmet need in global vaccine coverage against HIV and other global pathogens. Herein, we show that a simple dissolvable microneedle array (MA) delivery system preserves the immunogenicity of vaccines encoded by live recombinant human adenovirus type 5 (rAdHu5). Specifically, dried rAdHu5 MA immunization induced CD8(+) T-cell expansion and multifunctional cytokine responses equipotent with conventional injectable routes of immunization. Intravital imaging demonstrated MA cargo distributed both in the epidermis and dermis, with acquisition by CD11c(+) dendritic cells (DCs) in the dermis. The MA immunizing properties were attributable to CD11c(+) MHCII(hi) CD8α(neg) epithelial cell adhesion molecule (EpCAM(neg)) CD11b(+) langerin (Lang; CD207)(neg) DCs, but neither Langerhans cells nor Lang(+) DCs were required for CD8(+) T-cell priming. This study demonstrates an important technical advance for viral vaccine vectors progressing to the clinic and provides insights into the mechanism of CD8(+) T-cell priming by live rAdHu5 MAs.
authors: Peter Gorer Department of Immunobiology, King's College School of Medicine, London SE1 9RT, United Kingdom.
authors: Veronique
authors: V
authors: Bachy
authors: Catherine
authors: C
authors: Hervouet
authors: Pablo D
authors: PD
authors: Becker
authors: Laurent
authors: L
authors: Chorro
authors: Leo M
authors: LM
authors: Carlin
authors: Shanthi
authors: S
authors: Herath
authors: Timos
authors: T
authors: Papagatsias
authors: Jean-Baptiste
authors: JB
authors: Barbaroux
authors: Sea-Jin
authors: SJ
authors: Oh
authors: Adel
authors: A
authors: Benlahrech
authors: Takis
authors: T
authors: Athanasopoulos
authors: George
authors: G
authors: Dickson
authors: Steven
authors: S
authors: Patterson
authors: Sung-Yun
authors: SY
authors: Kwon
authors: Frederic
authors: F
authors: Geissmann
authors: Linda S
authors: LS
authors: Klavinskis
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000276:immunology*; D015703:Antigens, CD / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005434:Flow Cytometry; D005822:Genetic Vectors; D037181:Lectins, C-Type / Q000502:physiology*; D037241:Mannose-Binding Lectins / Q000502:physiology*; D018613:Microscopy, Confocal; D009339:Needles; D012867:Skin; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D015703:Antigens, CD; C121916:CD207 protein, human; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D014765:Viral Vaccines
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