Diphtheria toxoid dissolving microneedle vaccination: Adjuvant screening and effect of repeated-fractional dose administration

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dc.check.date2021-02-28
dc.check.infoAccess to this article is restricted until 12 months after publication by request of the publisher.en
dc.contributor.authorLeone, M.
dc.contributor.authorRomeijn, S.
dc.contributor.authorDu, G.
dc.contributor.authorLe Dévédec, S. E.
dc.contributor.authorVrieling, H.
dc.contributor.authorO'Mahony, Conor
dc.contributor.authorBouwstra, J. A.
dc.contributor.authorKersten, G.
dc.contributor.funderIntravacc, Netherlandsen
dc.date.accessioned2020-04-23T11:21:46Z
dc.date.available2020-04-23T11:21:46Z
dc.date.issued2020-02-28
dc.date.updated2020-04-23T10:12:26Z
dc.description.abstractIn this study the effect of repeated-fractional intradermal administration of diphtheria toxoid (DT) compared to a single administration in the presence or absence of adjuvants formulated in dissolving microneedles (dMNs) was investigated. Based on an adjuvant screening with a hollow microneedle (hMN) system, poly(I:C) and gibbsite, a nanoparticulate aluminum salt, were selected for further studies: they were co-encapsulated with DT in dMNs with either a full or fractional DT-adjuvant dose. Sharp dMNs were prepared regardless the composition and were capable to penetrate the skin, dissolve within 20 min and deposit the intended antigen-adjuvant dose, which remained in the skin for at least 5 h. Dermal immunization with hMN in repeated-fractional dosing (RFrD) resulted in a higher immune response than a single-full dose (SFD) administration. Vaccination by dMNs led overall to higher responses than hMN but did not show an enhanced response after RFrD compared to a SFD administration. Co-encapsulation of the adjuvant in dMNs did not increase the immune response further. Immunization by dMNs without adjuvant gave a comparable response to subcutaneously injected DT-AlPO4 in a 15 times higher dose of DT, as well as subcutaneous injected DT-poly(I:C) in a similar DT dose. Summarizing, adjuvant-free dMNs showed to be a promising delivery tool for vaccination performed in SFD administration.en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleid119182en
dc.identifier.citationLeone, M., Romeijn, S., Du, G., Le Dévédec, S. E., Vrieling, H., O'Mahony, C., Bouwstra, J. A. and Kersten, G. (2020) 'Diphtheria toxoid dissolving microneedle vaccination: Adjuvant screening and effect of repeated-fractional dose administration', International Journal of Pharmaceutics, 580, 119182 (11pp). doi: 10.1016/j.ijpharm.2020.119182en
dc.identifier.doi10.1016/j.ijpharm.2020.119182en
dc.identifier.eissn1873-3476
dc.identifier.endpage11en
dc.identifier.issn0378-5173
dc.identifier.journaltitleInternational Journal of Pharmaceuticsen
dc.identifier.startpage1en
dc.identifier.urihttps://hdl.handle.net/10468/9848
dc.identifier.volume580en
dc.language.isoenen
dc.publisherElsevier B.V.en
dc.rights© 2020, Elsevier B.V. All rights reserved. This manuscript version is made available under the CC BY-NC-ND 4.0 license.en
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectAluminum-based adjuvantsen
dc.subjectDiphtheria toxoiden
dc.subjectDissolving microneedlesen
dc.subjectIntradermal immunizationen
dc.subjectMicroneedlesen
dc.subjectRepeated-fractional vaccine deliveryen
dc.titleDiphtheria toxoid dissolving microneedle vaccination: Adjuvant screening and effect of repeated-fractional dose administrationen
dc.typeArticle (peer-reviewed)en
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