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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.