Langerin negative dendritic cells promote potent CD8+ T-cell priming after skin delivery of a recombinant adenovirus-based vaccine using microneedle arrays.

Abstract

Event Abstract Back to Event Langerin negative dendritic cells promote potent CD8+ T-cell priming after skin delivery of a recombinant adenovirus-based vaccine using microneedle arrays. Veronique S. Bachy1, Catherine Hervouet1, Pablo Becker1, Laurent Chorro2, Leo M. Carlin2, Shanthi Herath1, Sea-Jin Oh3, Sung-Yun Kwon3, Frederic Geissmann2 and Linda S. Klavinskis1* 1 Kings College London, Peter Gorer Department of Immunobiology, United Kingdom 2 Kings College London, Centre for Molecular and Cellular Biology of Inflammation, United Kingdom 3 TheraJect, United States Improving antigen immunogenicity and reducing dependence on the cold chain are key goals in vaccine development. To achieve this we have developed a simple dissolvable microneedle array (MA) delivery system, fabricated to confer properties that maintain the transduction competence of a live adenoviral vaccine vector within the microneedle matrix and provide tensile strength to enable skin penetration with subsequent vaccine delivery to DCs. Using recombinant Adenovirus (Ad5) vectors encoding either HIV-1 CN54 gag or ovalbumin in a biodegradable polymer matrix containing a disaccharide as preservative, we addressed both the utility of this approach in eliciting CD8+ T cell immunity and the DC populations critical to programming this response. Dried AdHu5 M.A. immunization in B6 mice induced CD8+ T cell expansion and multifunctional cytokine responses equipotent with conventional injectable routes of immunization. Intravital imaging of langerin-eGFP and CD11c-eGFP reporter mice, using flurochrome-linked dextran included with Ad5 in the needle matrix, demonstrated fluorescent M.A. cargo distributed both in the epidermis and dermis, with acquisition by dermal CD11c+ DC. Analysis of skin draining LNs after Ad5 vectored MA immunization, found no evidence for significant accumulation of CD11c+ MHCII hi Lang+ CD8a neg CD103neg Langerhans cells or presentation of Kb/SIINFEKL complexes by Lang+ DCs. Strikingly, we found a critical role for CD11c+ MHC IIhi CD8a neg EpCAM neg CD11b+ Lang neg DCs in priming the CD8+ T cell response, while Lang+ DCs were dispensable. These data shed new light on the early events following dermal vaccine delivery and have important implications for the development of viral vectored vaccines. Keywords: Dendritic Cells, langerin, dissolvable microneedle, Vaccine delivery, recombinant adenovirus vectored vaccine, skin delivery, CD8+ T cells, HIV-1 gag Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Translational immunology and immune intervention Citation: Bachy VS, Hervouet C, Becker P, Chorro L, Carlin LM, Herath S, Oh S, Kwon S, Geissmann F and Klavinskis LS (2013). Langerin negative dendritic cells promote potent CD8+ T-cell priming after skin delivery of a recombinant adenovirus-based vaccine using microneedle arrays.. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00708 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 14 Jun 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Linda S Klavinskis, Kings College London, Peter Gorer Department of Immunobiology, London, United Kingdom, linda.klavinskis@kcl.ac.uk Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Veronique S Bachy Catherine Hervouet Pablo Becker Laurent Chorro Leo M Carlin Shanthi Herath Sea-Jin Oh Sung-Yun Kwon Frederic Geissmann Linda S Klavinskis Google Veronique S Bachy Catherine Hervouet Pablo Becker Laurent Chorro Leo M Carlin Shanthi Herath Sea-Jin Oh Sung-Yun Kwon Frederic Geissmann Linda S Klavinskis Google Scholar Veronique S Bachy Catherine Hervouet Pablo Becker Laurent Chorro Leo M Carlin Shanthi Herath Sea-Jin Oh Sung-Yun Kwon Frederic Geissmann Linda S Klavinskis PubMed Veronique S Bachy Catherine Hervouet Pablo Becker Laurent Chorro Leo M Carlin Shanthi Herath Sea-Jin Oh Sung-Yun Kwon Frederic Geissmann Linda S Klavinskis Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.