Impact of dose, route, and composition on the immunogenicity of immune polyelectrolyte multilayers delivered on gold templates.
Impact of dose, route, and composition on the immunogenicity of immune polyelectrolyte multilayers delivered on gold templates.
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DOI：
10.1002/bit.26083
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发表时间：
2017-03
影响因子：
3.8
通讯作者：
Jewell CM
中科院分区：
文献类型：
--
作者：
Zhang P;Andorko JI;Jewell CM
生物材料疫苗提供了可用于传染病和癌症的新能力。我们最近开发了一种基于免疫信号自组装成免疫聚电解质多层膜（iPEMs）的新型疫苗平台。这些iPEM疫苗由肽抗原和作为分子佐剂的基于核酸的toll样受体激动剂（TLRas）静电组装而成。包被iPEMs的金纳米颗粒（AuNPs）在体外刺激效应细胞因子的分泌，并在小鼠体内扩增抗原特异性T细胞。在这里，我们研究了剂量、注射途径和分子佐剂的选择如何影响iPEMs在小鼠体内产生T细胞免疫和抗肿瘤反应的能力。采用皮内、皮下和肌肉注射三种注射途径和三种iPEM剂量水平。皮内注射诱导了最有效的抗原特异性T细胞反应，并且对于所有途径，反应水平都是剂量依赖性的。我们进一步发现，这些疫苗产生持久的记忆，在初始增强免疫方案后49天接种疫苗的小鼠中，有效的抗原特异性CD8+ T细胞回忆反应表明。在一种常见的外源性抗原黑色素瘤模型中，iPEM疫苗比等效的混合制剂更有效地减缓或阻止肿瘤生长。此外，与含有polyIC （TLR3a）的iPEMs相比，含有CpG-a tlr9a的iPEMs更有效。这些发现表明iPEMs能够增强对几种不同类型疫苗货物的反应，支持iPEMs作为一种简单的疫苗平台，利用可自组装或涂覆在底物上的免疫信号模仿其他纳米颗粒的有吸引力的特征。Biotechnol。Bioeng。2017;114: 423 - 431。©2016作者。《生物技术与生物工程》，Wiley期刊公司出版。
Biomaterial vaccines offer new capabilities that can be exploited for both infectious disease and cancer. We recently developed a novel vaccine platform based on self‐assembly of immune signals into immune polyelectrolyte multilayers (iPEMs). These iPEM vaccines are electrostatically assembled from peptide antigens and nucleic acid‐based toll‐like receptor agonists (TLRas) that serve as molecular adjuvants. Gold nanoparticles (AuNPs) coated with iPEMs stimulate effector cytokine secretion in vitro and expand antigen‐specific T cells in mice. Here we investigated how the dose, injection route, and choice of molecular adjuvant impacts the ability of iPEMs to generate T cell immunity and anti‐tumor response in mice. Three injection routes—intradermal, subcutaneous, and intramuscular—and three iPEM dosing levels were employed. Intradermal injection induced the most potent antigen‐specific T cell responses and, for all routes, the level of response was dose‐dependent. We further discovered that these vaccines generate durable memory, indicated by potent, antigen‐specific CD8+ T cell recall responses in mice challenged with vaccine 49 days after a prime‐boost immunization regimen. In a common exogenous antigen melanoma model, iPEM vaccines slowed or stopped tumor growth more effectively than equivalent ad‐mixed formulations. Further, iPEMs containing CpG—a TLR9a—were more potent compared with iPEMs containing polyIC, a TLR3a. These findings demonstrate the ability of iPEMs to enhance response to several different classes of vaccine cargos, supporting iPEMs as a simple vaccine platform that mimics attractive features of other nanoparticles using immune signals that can be self‐assembled or coated on substrates. Biotechnol. Bioeng. 2017;114: 423–431. © 2016 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals, Inc.
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影响因子：
7.8
作者：
Shirota H;Tross D;Klinman DM
通讯作者：
Klinman DM
影响因子：
15
作者：
Moyano, Daniel F;Goldsmith, Meir;Solfiell, David J;Landesman-Milo, Dalit;Miranda, Oscar R;Peer, Dan;Rotello, Vincent M
通讯作者：
Rotello, Vincent M
影响因子：
5.5
作者：
Goetsch, L;Plotnicky-Gilquin, H;Power, UF
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Power, UF
影响因子：
5.5
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Pittman, PR
通讯作者：
Pittman, PR
影响因子：
6.2
作者：
Shirota H;Klinman DM
通讯作者：
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