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Development of an Intranasal Vaccine To Prevent Urinary Tract Infection by Proteus mirabilis

机译:鼻内疫苗的开发,以预防变形杆菌感染泌尿道

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Proteus mirabilis commonly infects the complicated urinary tract and is associated with urolithiasis. Stone formation is caused by bacterial urease, which hydrolyzes urea to ammonia, causing local pH to rise, and leads to the subsequent precipitation of magnesium ammonium phosphate (struvite) and calcium phosphate (apatite) crystals. To prevent these infections, we vaccinated CBA mice with formalin-killed bacteria or purified mannose-resistant, Proteus-like (MR/P) fimbriae, a surface antigen expressed by P. mirabilis during experimental urinary tract infection, via four routes of immunization: subcutaneous, intranasal, transurethral, and oral. We assessed the efficacy of vaccination using the CBA mouse model of ascending urinary tract infection. Subcutaneous or intranasal immunization with formalin-killed bacteria and intranasal or transurethral immunization with purified MR/P fimbriae significantly protected CBA mice from ascending urinary tract infection by P. mirabilis (P < 0.05). To investigate the potential of MrpH, the MR/P fimbrial tip adhesin, as a vaccine, the mature MrpH peptide (residues 23 to 275, excluding the signal peptide), and the N-terminal receptor-binding domain of MrpH (residues 23 to 157) were overexpressed as C-terminal fusions to maltose-binding protein (MBP) and purified on amylose resins. Intranasal immunization of CBA mice with MBP-MrpH (residues 23 to 157) conferred effective protection against urinary tract infection by P. mirabilis (P < 0.002).
机译:奇异变形杆菌通常感染复杂的尿路,并与尿石症有关。细菌尿素酶引起结石形成,细菌尿素酶将尿素水解为氨,导致局部pH升高,并导致随后的磷酸镁铵(鸟粪石)和磷酸钙(磷灰石)晶体沉淀。为了防止这些感染,我们给CBA小鼠接种了福尔马林杀死的细菌或纯化的抗甘露糖的 Proteus 样(MR / P)菌毛,一种由 P表达的表面抗原。在实验性尿路感染过程中,通过皮下注射,鼻内注射,经尿道注射和口服四种免疫途径接种了奇异菌。我们使用升尿路感染的CBA小鼠模型评估了疫苗接种的功效。用福尔马林杀死的细菌进行皮下或鼻内免疫,以及用纯化的MR / P菌毛进行鼻内或经尿道免疫,可显着保护CBA小鼠免于 P引起的尿路感染。 ( P <0.05)。为了研究MrpH,MR / P纤维末端粘附素作为疫苗的潜力,成熟的MrpH肽(残基23至275,不包括信号肽)和MrpH的N端受体结合结构域(残基23至残基)。 157)过度表达为与麦芽糖结合蛋白(MBP)的C末端融合体,并在直链淀粉树脂上纯化。用MBP-MrpH(残基23至157)对CBA小鼠进行鼻内免疫可有效预防 P引起的尿路感染。奇迹 P <0.002)。

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