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

Bachy, V. et al. (2013) Langerin negative dendritic cells promote potent CD8+ T-cell priming by skin delivery of live adenovirus vaccine microneedle arrays. Proceedings of the National Academy of Sciences of the United States of America, 110(8), pp. 3041-3046. (doi: 10.1073/pnas.1214449110) (PMID:23386724) (PMCID:PMC3581957)

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+ MHCIIhi CD8αneg epithelial cell adhesion molecule (EpCAMneg) 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.

• Item Type: Articles
• Additional Information: This work is supported in part by the Bill and Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery and a European Union Sixth Framework Programme Network of Excellence (European Vaccines and Microbicides Enterprise) award.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Carlin, Dr Leo
• Authors: Bachy, V., Hervouet, C., Becker, P. D., Chorro, L., Carlin, L. M., Herath, S., Papagatsias, T., Barbaroux, J.-B., Oh, S.-J., Benlahrech, A., Athanasopoulos, T., Dickson, G., Patterson, S., Kwon, S.-Y., Geissmann, F., and Klavinskis, L. S.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Proceedings of the National Academy of Sciences of the United States of America
• Publisher: National Academy of Sciences
• ISSN: 0027-8424
• ISSN (Online): 1091-6490