Rapid Induction of Long-Lasting Systemic and Mucosal Immunity via Thermostable Microneedle-Mediated Chitosan Oligosaccharide-Encapsulated DNA Nanoparticles
Rapid Induction of Long-Lasting Systemic and Mucosal Immunity via Thermostable Microneedle-Mediated Chitosan Oligosaccharide-Encapsulated DNA Nanoparticles
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DOI：
10.1021/acsnano.3c09521
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发表时间：
2023-11-22
期刊：
影响因子：
17.1
通讯作者：
Sun，Caijun
中科院分区：
文献类型：
--
作者：
Li，Minchao;Yang，Li;Sun，Caijun
现有的大多数疫苗是通过肌肉注射(IM)提供的，通常与冷链配送下严格的储存要求和医务人员的专业管理有关，并且往往导致诱导较弱的粘膜免疫。在此背景下，我们报道了一种微针(MN)贴片，用于运送壳寡糖(COS)包裹的编码SARS-CoV-2刺突蛋白和核衣壳蛋白的DNA疫苗(DNA@COS)作为疫苗技术。与IM免疫相比，经MN介导的DNA疫苗皮内注射可有效诱导同等水平的SARS-CoV-2变异株中和抗体。令人惊讶的是，我们发现MN介导的皮内免疫诱导了更好的系统和粘膜T细胞免疫，增强了幅度、多功能性和持久性。重要的是，装载在MN贴片中的DNA@COS纳米疫苗可以在室温下保存至少1个月，而不会显著降低其免疫原性。机械上，我们的策略通过激活cGAS-STING介导的干扰素信号通路来增强树突状细胞的成熟和抗病毒免疫。总之，这项工作为快速开发一种易于管理和耐热的粘膜疫苗技术提供了有价值的见解。
Most existing vaccines, delivered by intramuscular injection (IM), are typically associated with stringent storage requirements under cold-chain distribution and professional administration by medical personnel and often result in the induction of weak mucosal immunity. In this context, we reported a microneedle (MN) patch to deliver chitosan oligosaccharide (COS)-encapsulated DNA vaccines (DNA@COS) encoding spike and nucleocapsid proteins of SARS-CoV-2 as a vaccination technology. Compared with IM immunization, intradermal administration via the MN-mediated DNA vaccine effectively induces a comparable level of neutralizing antibody against SARS-CoV-2 variants. Surprisingly, we found that MN-mediated intradermal immunization elicited superior systemic and mucosal T cell immunity with enhanced magnitude, polyfunctionality, and persistence. Importantly, the DNA@COS nanoparticle vaccine loaded in an MN patch can be stored at room temperature for at least 1 month without a significant decrease of its immunogenicity. Mechanically, our strategy enhanced dendritic cell maturation and antiviral immunity by activating the cGAS-STING-mediated IFN signaling pathway. In conclusion, this work provides valuable insights for the rapid development of an easy-to-administer and thermostable technology for mucosal vaccines.