Immunogenicity-Guided Design of an Acinetobacter baumanii Vaccine

IF 3.7 3区 医学 Q2 IMMUNOLOGY
Chenghua Zhu, Shuaiyuan Liang, Ning Yang, Shan Li, Jianpeng Xue, Runlu Zhou, Xiuwen Hong, Sixi Chen, Nan Gao, Qiang Du, Jianling Huang, Ganzhu Feng, Xingran Du
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Abstract

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.

Abstract Image

免疫原性导向的鲍曼不动杆菌疫苗设计
疫苗的开发是对抗多药耐药(MDR)鲍曼不动杆菌(鲍曼不动杆菌)感染的一种有希望和安全的策略。在这项研究中,我们设计并评估了基于树突状细胞(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鲍曼不动杆菌OmpW蛋白衍生的B细胞和t细胞表位,然后进行免疫学验证。利用6-氨基己酸将优势表位依次连接,合成多表位肽rOmpW。随后,将rommpw包裹在包覆中性粒细胞膜(NM)的聚乳酸-羟基乙酸(PLGA)纳米颗粒中,并用dc靶向肽(DCpep)对其表面进行功能化,构建仿生纳米疫苗dpep -NM-PLGA- rommpw。这种仿生纳米疫苗引发了强大的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作用。这些发现强调了这种仿生纳米疫苗作为鲍曼不动杆菌感染预防策略的转化潜力。
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来源期刊
CiteScore
8.30
自引率
3.70%
发文量
224
审稿时长
2 months
期刊介绍: The European Journal of Immunology (EJI) is an official journal of EFIS. Established in 1971, EJI continues to serve the needs of the global immunology community covering basic, translational and clinical research, ranging from adaptive and innate immunity through to vaccines and immunotherapy, cancer, autoimmunity, allergy and more. Mechanistic insights and thought-provoking immunological findings are of interest, as are studies using the latest omics technologies. We offer fast track review for competitive situations, including recently scooped papers, format free submission, transparent and fair peer review and more as detailed in our policies.
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