Dendritic cell-targeting DNA-based nasal adjuvants for protective mucosal immunity to Streptococcus pneumoniae.
Dendritic cell-targeting DNA-based nasal adjuvants for protective mucosal immunity to Streptococcus pneumoniae.
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DOI：
10.1111/1348-0421.12487
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发表时间：
2017-06
影响因子：
2.6
通讯作者：
Fujihashi K
中科院分区：
文献类型：
--
作者：
Kataoka K;Fukuyama Y;Briles DE;Miyake T;Fujihashi K
为了开发对主要肺部细菌感染有效的粘膜免疫的安全疫苗，必须考虑适当的疫苗抗原（Ags）、递送系统和无毒分子佐剂。这样的疫苗构建体可以诱导Ag特异性免疫应答，其提供针对粘膜感染的有效保护。特别是，已经表明，通过简单地将佐剂与细菌Ag混合，基于佐剂的粘膜疫苗制剂相对容易构建，并且所得疫苗可以引发保护性免疫。我们已经研究了基于DNA的鼻佐剂靶向粘膜树突状细胞（DC），以诱导Ag特异性粘膜和全身免疫反应，提供必要的保护，防止微生物病原体侵入我们的粘膜表面。在这篇综述中，我们首先介绍了一个质粒编码的Flt 3配体（pFL），这是一个分子的DC作为一个有效的佐剂粘膜免疫肺炎球菌感染的生长因子的cDNA。接下来，我们讨论了将未甲基化的CpG寡脱氧核苷酸与pFL一起与肺炎球菌Ag一起加入以保护免受肺炎球菌感染的可能性。为了做到这一点，我们使用肺炎球菌表面蛋白A作为疫苗，用于恢复衰老中的粘膜免疫。此外，我们还在肺炎球菌疫苗开发中使用了我们的具有磷酸胆碱-钥孔血蓝蛋白（PC-KLH）的鼻pFL佐剂系统，以成功地诱导对肺炎链球菌鼻携带的完全保护。最后，我们讨论的可能性，抗PC抗体诱导的鼻腔递送的pFL加PC-KLH可能起到预防动脉粥样硬化形成的保护作用，从而阻止随后的心血管疾病的发展。
In order to develop safe vaccines for effective mucosal immunity to major pulmonary bacterial infections, one must consider appropriate vaccine antigens (Ags), delivery systems and nontoxic molecular adjuvants. Such vaccine constructs can induce Ag-specific immune responses which provide effective protection from mucosal infections. In particular, it has been shown that adjuvant-based mucosal vaccine preparations are relatively easy to construct by simply mixing the adjuvant with the bacterial Ag, and the resulting vaccine can elicit protective immunity. We have studied DNA-based nasal adjuvants targeting mucosal dendritic cells (DCs) in order to induce Ag-specific mucosal and systemic immune responses that provide essential protection against microbial pathogens which invade our mucosal surfaces. In this review, we initially introduce a plasmid encoding the cDNA of Flt3 ligand (pFL), a molecule which is a growth factor for DCs as an effective adjuvant for mucosal immunity to pneumococcal infections. Next, we discuss the potential of adding unmethylated CpG oligodeoxynucleotide together with pFL together with a pneumococcal Ag for protection from pneumococcal infections. To do this, we have used pneumococcal surface protein A as vaccine for the restoration of mucosal immunity in aging. Further, we have also used our nasal pFL adjuvant system with phosphorylcholine-keyhole limpet hemocyanin (PC-KLH) in pneumococcal vaccine development, to successfully induce complete protection from nasal carriage by Streptococcus pneumoniae. Finally, we discuss the possibility that anti-PC antibodies induced by nasal delivery of pFL plus PC-KLH may play a protective role for prevention of atherogenesis and thus block the subsequent development of cardiovascular disease.
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