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皮内注射三价萨宾灭活脊髓灰质炎病毒疫苗的可溶性微针贴片诱导中和抗体。

Skin delivery of trivalent Sabin inactivated poliovirus vaccine using dissolvable microneedle patches induces neutralizing antibodies.

机构信息

School of Pharmacy, School of Biochemistry and Cell Biology, University College Cork, Cork, Ireland.

Intravacc (Institute for Translational Vaccinology), Bilthoven, The Netherlands.

出版信息

J Control Release. 2019 Oct;311-312:96-103. doi: 10.1016/j.jconrel.2019.08.039. Epub 2019 Sep 1.

Abstract

The cessation of the oral poliovirus vaccine (OPV) and the inclusion of inactivated poliovirus (IPV) into all routine immunization programmes, strengthens the need for new IPV options. Several novel delivery technologies are being assessed that permit simple yet efficacious and potentially dose-sparing administration of IPV. Current disadvantages of conventional liquid IPV include the dependence on cold chain and the need for injection, resulting in high costs, production of hazardous sharps waste and requiring sufficiently trained personnel. In the current study, a dissolvable microneedle (DMN) patch for skin administration that incorporates trivalent inactivated Sabin poliovirus vaccine (sIPV) was developed. Microneedles were physically stable in the ambient environment for at least 30 min and efficiently penetrated skin. Polio-specific IgG antibodies that were able to neutralize the virus were induced in rats upon administration using trivalent sIPV-containing microneedle patches. These sIPV-patch-induced neutralizing antibody responses were comparable to higher vaccine doses delivered intramuscularly for type 1 and type 3 poliovirus serotypes. Moreover, applying the patches to the flank elicited a significantly higher antibody response compared to their administration to the ear. This study progresses the development of a skin patch-based technology that would simplify vaccine administration of Sabin IPV and thereby overcome logistic issues currently constraining poliovirus eradication campaigns.

摘要

口服脊髓灰质炎疫苗(OPV)的停用和将灭活脊髓灰质炎病毒(IPV)纳入所有常规免疫规划,加强了对新型 IPV 选择的需求。正在评估几种新型的传递技术,这些技术允许简单但有效且具有潜在的节省剂量的 IPV 给药。传统液体 IPV 的当前缺点包括对冷链的依赖和需要注射,这导致成本高、产生危险的锐器废物,并需要足够训练有素的人员。在目前的研究中,开发了一种用于皮肤给药的可溶解微针(DMN)贴片,其中包含三价灭活萨宾脊髓灰质炎病毒疫苗(sIPV)。微针在环境温度下至少稳定 30 分钟,并且能够有效地穿透皮肤。在使用含有三价 sIPV 的微针贴片进行给药后,在大鼠中诱导出能够中和病毒的脊髓灰质炎特异性 IgG 抗体。这些 sIPV 贴片诱导的中和抗体反应与肌肉内更高疫苗剂量对 1 型和 3 型脊髓灰质炎病毒血清型的效果相当。此外,与耳部给药相比,将贴片贴到侧腹会引起更高的抗体反应。这项研究推进了基于皮肤贴片的技术的发展,该技术将简化对 Sabin IPV 的疫苗接种,从而克服目前限制脊髓灰质炎病毒根除运动的后勤问题。

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