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Diphtheria toxoid dissolving microneedle vaccination: Adjuvant screening and effect of repeated-fractional dose administration
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Date
2020-02-28
Authors
Leone, M.
Romeijn, S.
Du, G.
Le Dévédec, S. E.
Vrieling, H.
O'Mahony, Conor
Bouwstra, J. A.
Kersten, G.
Journal Title
Journal ISSN
Volume Title
Publisher
Elsevier B.V.
Published Version
Abstract
In 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.
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Keywords
Aluminum-based adjuvants , Diphtheria toxoid , Dissolving microneedles , Intradermal immunization , Microneedles , Repeated-fractional vaccine delivery
Citation
Leone, 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.2020.119182