Temporal release of a three-component protein subunit vaccine from polymer multilayers.
Temporal release of a three-component protein subunit vaccine from polymer multilayers.
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DOI：
10.1016/j.jconrel.2019.11.022
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发表时间：
2019-11
期刊：
影响因子：
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通讯作者：
D. S. Uppu;M. Turvey;Abdul Rahim Mohamed Sharif;Katell Bidet;Yanpu He;V. Ho;Anagha Tambe;J. Lescar;E. Tan;K. Fink;Jianzhu Chen;P. Hammond
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文献类型：
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作者：
D. S. Uppu;M. Turvey;Abdul Rahim Mohamed Sharif;Katell Bidet;Yanpu He;V. Ho;Anagha Tambe;J. Lescar;E. Tan;K. Fink;Jianzhu Chen;P. Hammond
持续的抗原和佐剂可用性已被证明可以改善接种疫苗后的抗病毒免疫反应。使用微针经皮注射疫苗也显示出了希望，可能与蚊媒病毒特别相关。我们的目标是将这些特性结合在一起，创造一种基于微针阵列(PSMN)的三组分蛋白质亚单位疫苗，用于使用逐层组装(LBL)经皮递送。制备了聚合物多层薄膜，以共同传递三种不同化学成分的疫苗组分的模型组合，即登革病毒包膜蛋白结构域III(EDIII)亚单位抗原和两种佐剂、双链RNA(聚(肌苷：胞二酸)(PolyI：C))和两亲性六肽Pam3CSK4。在将PSMN应用于皮肤后，植入的薄膜促进了单个疫苗成分从聚合物多层膜中的持续和暂时释放。通过调节LBL的组成和结构，皮肤中的成分释放曲线可以独立调整，以允许从几天到两周的时间释放佐剂和抗原。在体内、小鼠和体外人皮肤模型中，抗原提呈细胞从植入的疫苗膜中摄取抗原和佐剂。总体而言，我们认为这种模块化疫苗策略为提高蛋白质亚单位疫苗的免疫原性提供了设计原则。
Sustained antigen and adjuvant availability have been shown to improve antiviral immune responses following vaccination. Transcutaneous delivery of vaccines using microneedles has also shown promise and may be particularly relevant for mosquito-borne viruses. We aim to combine these traits to create a three-component Protein Subunit vaccine on Microneedle Arrays (PSMNs) for transcutaneous delivery using layer-by-layer (LbL) assembly. Polymer multilayer thin films were generated to co-deliver a model combination of three chemically distinct vaccine components, a dengue virus Envelope protein Domain III (EDIII) subunit antigen and two adjuvants, a double-stranded RNA (Poly (inosinic:cytidylic acid) (PolyI:C)) and an amphiphilic hexapeptide, Pam3CSK4. Following application of PSMNs to the skin, implanted thin films facilitated sustained and temporal release of individual vaccine components from polymer multilayers. By modulating LbL composition and architecture, component release profiles in the skin could be independently tuned to allow release of adjuvants and antigen from days up to two weeks. Uptake of antigen and adjuvant from implanted vaccine films by antigen-presenting cells was demonstrated using in vivo mouse and ex vivo human skin models. Overall, we believe that such modular vaccine strategies offer design principles for enhancing the immunogenicity of protein subunit vaccines.