title: Induction of CD8(+) T cell responses and protective efficacy following microneedle-mediated delivery of a live adenovirus-vectored malaria vaccine.
abstract: There is an urgent need for improvements in vaccine delivery technologies. This is particularly pertinent for vaccination programmes within regions of limited resources, such as those required for adequate provision for disposal of used needles. Microneedles are micron-sized structures that penetrate the stratum corneum of the skin, creating temporary conduits for the needle-free delivery of drugs or vaccines. Here, we aimed to investigate immunity induced by the recombinant simian adenovirus-vectored vaccine ChAd63.ME-TRAP; currently undergoing clinical assessment as a candidate malaria vaccine, when delivered percutaneously by silicon microneedle arrays. In mice, we demonstrate that microneedle-mediated delivery of ChAd63.ME-TRAP induced similar numbers of transgene-specific CD8(+) T cells compared to intradermal (ID) administration with needle-and-syringe, following a single immunisation and after a ChAd63/MVA heterologous prime-boost schedule. When mice immunised with ChAd63/MVA were challenged with live Plasmodium berghei sporozoites, microneedle-mediated ChAd63.ME-TRAP priming demonstrated equivalent protective efficacy as did ID immunisation. Furthermore, responses following ChAd63/MVA immunisation correlated with a specific design parameter of the array used ('total array volume'). The level of transgene expression at the immunisation site and skin-draining lymph node (dLN) was also linked to total array volume. These findings have implications for defining silicon microneedle array design for use with live, vectored vaccines.
authors.affiliation: The Jenner Institute, University of Oxford, Roosevelt Drive, Oxford, United Kingdom. Electronic address: f.pearson@uq.edu.au.
authors.forename: Frances E
authors.initials: FE
authors.lastname: Pearson
authors.affiliation: Tyndall National Institute, Lee Maltings, University College Cork, Cork, Ireland. Electronic address: conor.omahony@tyndall.ie.
authors.forename: Conor
authors.initials: C
authors.lastname: O'Mahony
authors.affiliation: School of Pharmacy, University College Cork, Cork, Ireland; Department of Pharmacology, University College Cork, Cork, Ireland. Electronic address: anne.moore@ucc.ie.
authors.forename: Anne C
authors.initials: AC
authors.lastname: Moore
authors.affiliation: The Jenner Institute, University of Oxford, Roosevelt Drive, Oxford, United Kingdom. Electronic address: adrian.hill@ndm.ox.ac.uk.
authors.forename: Adrian V S
authors.initials: AV
authors.lastname: Hill
mesh_terms: D000261:Adenoviruses, Simian / Q000235:genetics; D000279:Administration, Cutaneous; D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D007271:Injections, Intradermal; D008288:Malaria / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D051379:Mice; D009339:Needles; D010962:Plasmodium berghei / Q000276:immunology; D010963:Plasmodium falciparum / Q000276:immunology; D012825:Silicon; D034101:Sporozoites / Q000276:immunology; D019076:Transgenes; D014611:Vaccination / Q000379:methods*; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D017780:Malaria Vaccines; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; D012825:Silicon
keywords: Adenovirus; Challenge; Malaria; Microneedle; Skin vaccination; T cell