Department of Molecular Biology, Pasteur Institute of Iran, Pasteur Ave., Tehran 13164, Iran.
National Cell Bank of Iran, Pasteur Institute of Iran, Pasteur Ave., Tehran 13164, Iran.
Mol Immunol. 2015 Apr;64(2):285-94. doi: 10.1016/j.molimm.2014.12.008. Epub 2015 Jan 4.
Urinary tract infections (UTIs) caused by Uropathogenic Escherichia coli (UPEC) and Proteus mirabilis are among the most common infections in the world. Currently there are no vaccines available to confer protection against UTI in humans. In this study, the immune responses and protection of FimH of UPEC with MrpH antigen of P. mirabilis in different vaccine formulations with and without MPL adjuvant were assessed. Mice intranasally immunized with the novel fusion protein MrpH·FimH induced a significant increase in IgG and IgA in serum, nasal wash, vaginal wash, and urine samples. Mice immunized with fusion MrpH·FimH also showed a significant boost in cellular immunity. Addition of MPL as the adjuvant enhanced FimH and MrpH specific humoral and cellular responses in both systemic and mucosal samples. Vaccination with MrpH·FimH alone or in combination with MPL showed the highest efficiency in clearing bladder and kidney infections in mice challenged with UPEC and P. mirabilis. These findings may indicate that the protection observed correlates with the systemic, mucosal and cellular immune responses induced by vaccination with these preparations. Our data suggest MrpH·FimH fusion protein with or without MPL as adjuvant could be potential vaccine candidates for elimination of UPEC and P. mirabilis. These data altogether are promising and these formulations are good candidates for elimination of UPEC and P. mirabilis.
尿路致病性大肠杆菌(UPEC)和奇异变形杆菌引起的尿路感染(UTI)是世界上最常见的感染之一。目前,尚无针对人类尿路感染的疫苗。在这项研究中,评估了不同疫苗配方中 FimH 和 MrpH 抗原与或不与 MPL 佐剂联合使用时对 UPEC 的免疫反应和保护作用。用新型融合蛋白 MrpH·FimH 鼻腔免疫的小鼠,诱导血清、鼻腔冲洗液、阴道冲洗液和尿液样本中 IgG 和 IgA 显著增加。用融合 MrpH·FimH 免疫的小鼠也显示出细胞免疫的显著增强。添加 MPL 作为佐剂增强了系统和粘膜样本中 FimH 和 MrpH 特异性体液和细胞反应。单独用 MrpH·FimH 或与 MPL 联合接种,在预防 UPEC 和奇异变形杆菌引起的膀胱和肾脏感染方面显示出最高的效率。这些发现可能表明观察到的保护与这些制剂接种引起的全身、粘膜和细胞免疫反应相关。我们的数据表明,MrpH·FimH 融合蛋白与或不与 MPL 作为佐剂可能是消除 UPEC 和奇异变形杆菌的潜在疫苗候选物。这些数据表明这些制剂有希望成为消除 UPEC 和奇异变形杆菌的良好候选物。