基于鲍曼不动杆菌纳米疫苗Chitosan-PLGA-rOmp22粘膜免疫效应的机制研究

多重耐药及泛耐药鲍曼不动杆菌（Ab）感染的治疗成为临床棘手难题，开发针对Ab的疫苗变得尤为迫切。鼻粘膜免疫具有操作简单、安全性好及抗原生物利用度高等优势，被认为是一种极有前途的免疫途径。本课题组前期制备了Ab纳米疫苗Chitosan-PLGA-rOmp22，经鼻粘膜免疫BALB/c小鼠，可诱导机体产生免疫保护应答、发挥免疫保护效应，但具体机制尚未明确。本课题拟在前期研究的基础上，通过体内外实验证实如下科学假说：Ab纳米疫苗CS-PLGA-rOmp22经鼻粘膜免疫后，通过提高鼻粘膜相关淋巴组织（NALT）中DCs细胞的抗原提呈能力，促进MHC-II类分子将抗原提呈给CD4+T细胞，促使CD4+T活化并分化为Th2细胞，继而促进初始B细胞分化为浆细胞，产生特异性抗体，对Ab菌攻击产生保护作用。本项目的实施，将为该纳米疫苗的进一步开发甚至临床转化提供实验依据，也为减少Ab在医院的流行提供新策略。

The development of vaccines is a promising and cost-effective strategy to prevent emerging multi-drug resistant (MDR) Acinetobacter baumannii (A. baumannii) infections. Intranasal immunization is considered as a promising immune approach as its advantages of simple operation, safety and high bioavailability of antigens. In our previous study, we prepared a nanovaccine chitosan-PLGA-rOmp22, which could induce immunoprotective efficacy against A. baumannii after intranasl immunization in BALB/c mice. In this study, in vivo and in vitro assays will be carried out to confirm the hypothesis as follow : Intranasl immunization with CS-PLGA-rOmp22 could improve the antigen presenting ability of DCs in nasal mucosa associated lymphoid tissue (NALT). The antigen was presented to CD4+T cells via the MHC-II pathway, which will promote the activation and differentiation of T helper cells, and further promote the differentiate of initial B lymphocytes into plasma cells and produce antigen specific antibodies against A. baumannii. The implementation of this study will provide experimental basis for the further development and even clinical transformation of this nanovaccine, and also provide new strategy to reduce the prevalence of A. baumannii in hospitals.