Zhu Chenghua, Liang Shuaiyuan, Yang Ning, Li Shan, Xue Jianpeng, Zhou Runlu, Hong Xiuwen, Chen Sixi, Gao Nan, Du Qiang, Huang Jianling, Feng Ganzhu, Du Xingran
Department of Respiratory Medicine, Pukou Hospital of Chinese Medicine Affiliated to China Pharmaceutical University, Nanjing, Jiangsu, China.
Department of Pulmonary and Critical Care Medicine, The Second Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu, China.
Eur J Immunol. 2025 Jul;55(7):e70019. doi: 10.1002/eji.70019.
The development of vaccines represents a promising and safe strategy to combat multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) infections. In this study, we designed and evaluated a dendritic cell (DC)-targeting multiepitope peptide-based biomimetic nanovaccine for its immunogenicity and protective efficacy in a murine model. Bioinformatics tools were employed to predict and screen B- and T-cell epitopes derived from the OmpW protein of A. baumannii, followed by immunological validation. The dominant epitopes were sequentially linked using 6-aminocaproic acid to synthesize a multiepitope peptide, rOmpW. Subsequently, rOmpW was encapsulated within polylactic-co-glycolic acid (PLGA) nanoparticles coated with neutrophil membranes (NM), and the surface was functionalized with a DC-targeting peptide (DCpep) to construct the biomimetic nanovaccine, DCpep-NM-PLGA-rOmpW. This biomimetic nanovaccine elicited robust Th1 and Th17 cellular immune responses, as well as humoral immunity, and demonstrated significant protective efficacy in a murine model of acute lethal pneumonia caused by A. baumannii. These findings underscore the translational potential of this biomimetic nanovaccine as a prophylactic strategy against A. baumannii infections.
疫苗的研发是对抗多重耐药鲍曼不动杆菌（A. baumannii）感染的一种有前景且安全的策略。在本研究中，我们设计并评估了一种基于树突状细胞（DC）靶向多表位肽的仿生纳米疫苗在小鼠模型中的免疫原性和保护效果。利用生物信息学工具预测和筛选源自鲍曼不动杆菌OmpW蛋白的B细胞和T细胞表位，随后进行免疫学验证。使用6-氨基己酸将优势表位依次连接以合成多表位肽rOmpW。随后，将rOmpW封装在涂有中性粒细胞膜（NM）的聚乳酸-乙醇酸共聚物（PLGA）纳米颗粒中，并使用DC靶向肽（DCpep）对表面进行功能化，以构建仿生纳米疫苗DCpep-NM-PLGA-rOmpW。这种仿生纳米疫苗引发了强烈的Th1和Th17细胞免疫反应以及体液免疫，并在鲍曼不动杆菌引起的急性致死性肺炎小鼠模型中显示出显著的保护效果。这些发现强调了这种仿生纳米疫苗作为预防鲍曼不动杆菌感染的策略的转化潜力。
