Microneedle array design determines the induction of protective memory CD8+ T Cell responses induced by a recombinant live malaria vaccine in mice

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dc.contributor.authorCarey, John B.
dc.contributor.authorPearson, Frances E.
dc.contributor.authorVrdoljak, Anto
dc.contributor.authorMcGrath, Marie G.
dc.contributor.authorCrean, Abina M.
dc.contributor.authorWalsh, Patrick T.
dc.contributor.authorDoody, Timothy
dc.contributor.authorO'Mahony, Conor
dc.contributor.authorHill, Adrian V. S.
dc.contributor.authorMoore, Anne C.
dc.contributor.funderEnterprise Irelanden
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderMedical Research Council, United Kingdomen
dc.date.accessioned2019-11-19T10:19:45Z
dc.date.available2019-11-19T10:19:45Z
dc.date.issued2011-07-25
dc.description.abstractBackground: Vaccine delivery into the skin has received renewed interest due to ease of access to the immune system and microvasculature, however the stratum corneum (SC), must be breached for successful vaccination. This has been achieved by removing the SC by abrasion or scarification or by delivering the vaccine intradermally (ID) with traditional needle-and-syringes or with long microneedle devices. Microneedle patch-based transdermal vaccine studies have predominantly focused on antibody induction by inactivated or subunit vaccines. Here, our principal aim is to determine if the design of a microneedle patch affects the CD8+ T cell responses to a malaria antigen induced by a live vaccine. Methodology and Findings Recombinant modified vaccinia virus Ankara (MVA) expressing a malaria antigen was percutaneously administered to mice using a range of silicon microneedle patches, termed ImmuPatch, that differed in microneedle height, density, patch area and total pore volume. We demonstrate that microneedle arrays that have small total pore volumes induce a significantly greater proportion of central memory T cells that vigorously expand to secondary immunization. Microneedle-mediated vaccine priming induced significantly greater T cell immunity post-boost and equivalent protection against malaria challenge compared to ID vaccination. Notably, unlike ID administration, ImmuPatch-mediated vaccination did not induce inflammatory responses at the site of immunization or in draining lymph nodes. Conclusions/Significance: This study demonstrates that the design of microneedle patches significantly influences the magnitude and memory of vaccine-induced CD8+ T cell responses and can be optimised for the induction of desired immune responses. Furthermore, ImmuPatch-mediated delivery may be of benefit to reducing unwanted vaccine reactogenicity. In addition to the advantages of low cost and lack of pain, the development of optimised microneedle array designs for the induction of T cell responses by live vaccines aids the development of solutions to current obstacles of immunization programmes.en
dc.description.sponsorshipCFTD 07/117; NAP156; NAP170; G0600311en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleide22442en
dc.identifier.citationCarey, J.B., Pearson, F.E., Vrdoljak, A., McGrath, M.G., Crean, A.M., Walsh, P.T., Doody, T., O'Mahony, C., Hill, A.V. and Moore, A.C., 2011. Microneedle array design determines the induction of protective memory CD8+ T cell responses induced by a recombinant live malaria vaccine in mice. PLoS One, 6(7), (e22442). DOI:10.1371/journal.pone.0022442en
dc.identifier.doi10.1371/journal.pone.0022442en
dc.identifier.eissn1932-6203
dc.identifier.endpage13en
dc.identifier.issued7en
dc.identifier.journaltitlePLoS ONEen
dc.identifier.startpage1en
dc.identifier.urihttps://hdl.handle.net/10468/9063
dc.identifier.volume6en
dc.language.isoenen
dc.publisherPLoSen
dc.relation.urihttps://journals.plos.org/plosone/article?id=10.1371/journal.pone.0022442
dc.rights© 2011 Carey et alen
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectVaccine deliveryen
dc.subjectMicroneedleen
dc.subjectCD8+ T cell responsesen
dc.titleMicroneedle array design determines the induction of protective memory CD8+ T Cell responses induced by a recombinant live malaria vaccine in miceen
dc.typeArticle (peer-reviewed)en
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