A Live-Attenuated Vaccine for the Treatment of Urinary Tract Infection by Uropathogenic Escherichia coli
A Live-Attenuated Vaccine for the Treatment of Urinary Tract Infection by Uropathogenic Escherichia coli
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DOI：
10.1086/599839
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发表时间：
2009-07-15
影响因子：
6.4
通讯作者：
Klumpp, David J.
中科院分区：
文献类型：
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作者：
Billips, Benjamin K.;Yaggie, Ryan E.;Klumpp, David J.
尿路致病性大肠杆菌是引起尿路感染的主要原因。我们最近证明，O抗原连接酶基因waaL的缺失，从尿路致病性大肠杆菌。大肠杆菌分离株NU 14产生刺激增强的尿路上皮细胞因子分泌的菌株。由于增强的先天免疫应答在疫苗开发中是感兴趣的，我们检查了NU 14 Δ waaL作为尿路感染疫苗的治疗潜力。NU 14 DwaaL刺激小鼠巨噬细胞分泌增强的白细胞介素-6，与野生型分泌相比。通过滴注到膀胱中接种疫苗的小鼠产生了保护性反应，防止了NU 14膀胱攻击后的持续定植，但NU 14 DwaaL未能持续定植在小鼠膀胱中。用疫苗株接种保护小鼠免受广泛的临床尿路致病性E.大肠杆菌分离物，并产生持续>= 8周的免疫力。因此，NU 14 DwaaL是治疗和预防尿路致病性大肠杆菌引起的急性和复发性尿路感染的候选减毒活疫苗。杆菌
Uropathogenic Escherichia coli are the leading cause of urinary tract infection. We recently demonstrated that deletion of the O antigen ligase gene, waaL, from the uropathogenic E. coliisolate NU14 results in a strain that stimulates enhanced urothelial cytokine secretion. Because enhanced innate immune responses are of interest in vaccine development, we examined the therapeutic potential of NU14 Delta waaL as a vaccine for urinary tract infection. NU14 DwaaL stimulated enhanced interleukin-6 secretion by mouse macrophages, compared with secretion by the wild type. Mice vaccinated via instillation into the bladder developed protective responses that prevented persistent colonization after bladder challenge with NU14, yet NU14 DwaaL failed to persistently colonize the mouse bladder. Inoculation with the vaccine strain protected mice against challenge with a broad range of clinical uropathogenic E. coli isolates and produced immunity that lasted >= 8 weeks. Therefore, NU14 DwaaL is a candidate live-attenuated vaccine for the treatment and prevention of acute and recurrent urinary tract infection by caused by uropathogenic E. coli.