Controlled release of a model vaccine by nanoporous ceramic microneedle arrays

Controlled release of a model vaccine by nanoporous ceramic microneedle arrays
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DOI:
10.1016/j.ijpharm.2015.06.025
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发表时间:
2015-08-01
影响因子:
5.8
通讯作者:
Luttge, Regina
Luttge, Regina
中科院分区:
医学2区
文献类型:
--
作者:
Boks, Martine A.;Unger, Wendy W. J.;Luttge, Regina

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目前的疫苗接种技术可以从新型陶瓷纳米孔微针阵列(npMNA)的使用中得到进步,这种材料可以作为疫苗的储存库。此外,npMNA将通过更精确地到达皮肤树突状细胞(T细胞和B细胞免疫的启动者)来提高疫苗效力。在本研究中,我们通过在体内使用OVA(257-264)多肽与激动性抗cd40抗体混合作为佐剂来评估npMNAs疫苗接种的效果。npMNA诱导ova特异性CD8(+) T细胞的频率与针刺皮下注射诱导的频率相当。然而,只有当使用两种npMNAs扩大疫苗接种区域时,诱导的ifn - γ特异性效应CD8(+) T细胞的频率与通过针头注射器注射诱导的频率相当。在人离体皮肤外植体模型中,对疫苗从npMNA释放的分析表明,OVA(257-264)肽确实在皮内释放,并且随着npMNA在人皮肤上应用时间的延长,释放量也增加。总之,我们的研究证明了npMNA在人皮肤疫苗递送和体内诱导CD8(+)效应T细胞反应方面的潜力。(C) 2015 Elsevier B.V.版权所有
Current vaccination technology can advance from the use of novel ceramic nanoporous microneedle arrays (npMNA), where the material serves as a storage reservoir for vaccines. Moreover, npMNA will enhance vaccine efficacy by more precisely reaching skin dendritic cells, the kickstarters of T and B cell immunity. In the present study we assessed the efficacy of vaccination using npMNAs by in vivo application of OVA(257-264) peptides mixed with agonistic anti-CD40 antibodies as adjuvant. The induction of OVA-specific CD8(+) T cells via npMNA was comparable with the frequency induced via intradermal injection using needle-syringe. However, only when expanding the vaccination area by using two npMNAs the frequencies of induced IFN-gamma-specific effector CD8(+) T cells were comparable with those induced via needle-syringe injection. Analysis of vaccine release from npMNA in a human ex vivo skin explant model revealed that OVA(257-264) peptides were indeed delivered intradermal, and release also increased by prolonging the npMNA application time on the human skin. Together, our studies demonstrate the potential of npMNA for vaccine delivery in human skin and in vivo induction of CD8(+) effector T cell responses. (C) 2015 Elsevier B.V. All rights reserved.