铜绿假单胞菌
微生物学
抗生素
接种疫苗
免疫系统
细菌
致病菌
革兰氏阴性菌
免疫
生物
肺炎
毒力
体内
免疫学
医学
生物技术
大肠杆菌
基因
内科学
生物化学
遗传学
作者
Xiaoli Wei,Danni Ran,Anaamika Campeau,Crystal Xiao,Jiarong Zhou,Diana Dehaini,Yao Jiang,Ashley V. Kroll,Qiangzhe Zhang,Weiwei Gao,David J. Gonzalez,Ronnie H. Fang,Liangfang Zhang
出处
期刊:Nano Letters
[American Chemical Society]
日期:2019-06-07
卷期号:19 (7): 4760-4769
被引量:64
标识
DOI:10.1021/acs.nanolett.9b01844
摘要
Infections caused by multidrug-resistant Gram-negative bacteria have emerged as a major threat to public health worldwide. The high mortality and prevalence, along with the slow pace of new antibiotic discovery, highlight the necessity for new disease management paradigms. Here, we report on the development of a multiantigenic nanotoxoid vaccine based on macrophage membrane-coated nanoparticles for eliciting potent immunity against pathogenic Pseudomonas aeruginosa. The design of this biomimetic nanovaccine leverages the specific role of macrophages in clearing pathogens and their natural affinity for various virulence factors secreted by the bacteria. It is demonstrated that the macrophage nanotoxoid is able to display a wide range of P. aeruginosa antigens, and the safety of the formulation is confirmed both in vitro and in vivo. When used to vaccinate mice via different administration routes, the nanotoxoid is capable of eliciting strong humoral immune responses that translate into enhanced protection against live bacterial infection in a pneumonia model. Overall, the work presented here provides new insights into the design of safe, multiantigenic antivirulence vaccines using biomimetic nanotechnology and the application of these nanovaccines toward the prevention of difficult-to-treat Gram-negative infections.
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