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Langerin negative dendritic cells promote potent CD8⁺ T-cell priming by skin delivery of live adenovirus vaccine microneedle arrays

Bachy, Veronique, Hervouet, Catherine, Becker, Pablo D., Chorro, Laurent, Carlin, Leo M., Herath, Shanthi, Papagatsias, Timos, Barbaroux, Jean-Baptiste, Oh, Sea-Jin, Benlahrech, Adel, Athanasopoulos, Takis, Dickson, George, Patterson, Steven, Kwon, Sung-Yun, Geissmann, Frederic, Klavinskis, Linda S.
Proceedings of the National Academy of Sciences of the United States of America 2013 v.110 no.8 pp. 3041-3046
CD8-positive T-lymphocytes, Human adenovirus C, Human immunodeficiency virus, Langerhans cells, cell adhesion, cold, cytokines, dermis, epithelial cells, image analysis, immune response, immunization, nucleic acids, pathogens, protein structure, transcription (genetics), viral vaccines, viruses
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.