DNA vaccine encoding OmpA and Pal from Acinetobacter baumannii efficiently protects mice against pulmonary infection

DNA vaccine encoding OmpA and Pal from Acinetobacter baumannii efficiently protects mice against pulmonary infection
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编码鲍曼不动杆菌 OmpA 和 Pal 的 DNA 疫苗可有效保护小鼠免受肺部感染

DOI:
10.1007/s11033-019-04994-2
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发表时间:
2019-10-01
影响因子:
2.8
通讯作者:
Wang, Xingyong
Wang, Xingyong
中科院分区:
生物学4区
文献类型:
--
作者:
Lei, Langhuan;Yang, Feng;Wang, Xingyong

文献摘要

被引文献

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鲍曼不动杆菌(A. baumannii)是一种机会性病原体,可引起医院危重患者的肺部、血液和大脑严重感染,每年导致相当高的死亡率。由于多重耐药甚至泛耐药菌株的迅速出现,传统的抗生素治疗越来越难以治愈鲍曼不动杆菌感染,迫切需要替代策略来对抗鲍曼不动杆菌感染。在本研究中,我们开发了编码鲍曼不动杆菌OmpA和Pal两种抗原的DNA疫苗,并进一步评估了其免疫原性和保护功效。结果表明,该DNA疫苗在小鼠肺炎模型中对急性鲍曼不动杆菌感染表现出显着的免疫保护功效,并且当免疫小鼠受到鲍曼不动杆菌临床菌株攻击时观察到交叉保护功效。 DNA 疫苗免疫诱导高水平的体液反应和混合 Th1/Th2/Th17 细胞反应,通过减少肺部细菌负荷和病理学,并降低 BALF 中炎症细胞因子表达和炎症细胞浸润水平,防止致命细菌的攻击。这些结果表明,通过DNA疫苗预防鲍曼不动杆菌感染是可能的,并且OmpA和Pal都可以作为有希望的候选抗原。
Acinetobacter baumannii (A. baumannii) is an opportunistic pathogen that causes serious infections in the lungs, blood, and brain in critically ill hospital patients, resulting in considerable mortality rates every year. Due to the rapid appearance of multi-drug resistance or even pan-drug resistance isolates, it is becoming more and more difficult to cure A. baumannii infection by traditional antibiotic treatment, alternative strategies are urgently required to combat A. baumannii infection. In this study, we developed a DNA vaccine encoding two antigens from A. baumannii, OmpA and Pal, and the immunogenicity and protective efficacy was further evaluated. The results showed that the DNA vaccine exhibited significant immune protective efficacy against acute A. baumannii infection in a mouse pneumonia model, and cross protective efficacy was observed when immunized mice were challenged with clinical strains of A. baumannii. DNA vaccine immunization induced high level of humoral response and a mixed Th1/Th2/Th17 cellular response, which protect against lethal bacterial challenges by decreased bacterial loads and pathology in the lungs, and reduced level of inflammatory cytokines expression and inflammatory cell infiltration in BALF. These results demonstrated that it is possible to prevent A. baumannii infection by DNA vaccine and both OmpA and Pal could be serve as promising candidate antigens.