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高密度微针阵列给药于大鼠皮肤低剂量三价灭活脊髓灰质炎疫苗可引发强烈的中和抗体反应。

High-density microprojection array delivery to rat skin of low doses of trivalent inactivated poliovirus vaccine elicits potent neutralising antibody responses.

机构信息

Delivery of Drugs and Genes Group (D2G2) Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland, QLD 4072, Australia.

Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Queensland, Australia.

出版信息

Sci Rep. 2017 Oct 3;7(1):12644. doi: 10.1038/s41598-017-13011-0.

Abstract

To secure a polio-free world, the live attenuated oral poliovirus vaccine (OPV) will eventually need to be replaced with inactivated poliovirus vaccines (IPV). However, current IPV delivery is less suitable for campaign use than OPV, and more expensive. We are progressing a microarray patch delivery platform, the Nanopatch, as an easy-to-use device to administer vaccines, including IPV. The Nanopatch contains an ultra-high density array (10,000/cm) of short (~230 μm) microprojections that delivers dry coated vaccine into the skin. Here, we compare the relative immunogenicity of Nanopatch immunisation versus intramuscular injection in rats, using monovalent and trivalent formulations of IPV. Nanopatch delivery elicits faster antibody response kinetics, with high titres of neutralising antibody after just one (IPV2) or two (IPV1 and IPV3) immunisations, while IM injection requires two (IPV2) or three (IPV1 and IPV3) immunisations to induce similar responses. Seroconversion to each poliovirus type was seen in 100% of rats that received ~1/40th of a human dose of IPV delivered by Nanopatch, but not in rats given ~1/8th or ~1/40th dose by IM injection. Ease of administration coupled with dose reduction observed in this study suggests the Nanopatch could facilitate inexpensive IPV vaccination in campaign settings.

摘要

为了确保无脊髓灰质炎世界的安全,减毒口服脊髓灰质炎疫苗(OPV)最终将需要被灭活脊髓灰质炎疫苗(IPV)所取代。然而,目前的 IPV 接种方式不如 OPV 适合大规模接种,且成本更高。我们正在开发一种微阵列贴片输送平台——Nanopatch,作为一种易于使用的疫苗接种工具,包括 IPV。Nanopatch 包含一个超高密度的短微针(~230μm)阵列(10,000/cm),可将干燥涂层的疫苗递送至皮肤内。在这里,我们比较了 Nanopatch 免疫接种与肌肉内注射在大鼠中的相对免疫原性,使用了单价和三价 IPV 制剂。Nanopatch 接种引发了更快的抗体反应动力学,仅进行一次(IPV2)或两次(IPV1 和 IPV3)免疫接种后即可产生高滴度的中和抗体,而肌肉内注射则需要进行两次(IPV2)或三次(IPV1 和 IPV3)免疫接种才能产生类似的反应。接受 Nanopatch 接种的大鼠中,有 100%的大鼠对每一种脊髓灰质炎病毒类型都产生了血清转化,而接受肌肉内注射的大鼠则没有。在这项研究中,观察到的给药简便性和剂量减少提示 Nanopatch 可促进在大规模接种环境中进行廉价的 IPV 接种。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a82/5626768/db3897492897/41598_2017_13011_Fig1_HTML.jpg

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