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

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Leone, M.
Romeijn, S.
Du, G.
Le Dévédec, S. E.
Vrieling, H.
O'Mahony, Conor
Bouwstra, J. A.
Kersten, G.
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Elsevier B.V.
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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.
Aluminum-based adjuvants , Diphtheria toxoid , Dissolving microneedles , Intradermal immunization , Microneedles , Repeated-fractional vaccine delivery
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