Saz-Leal Paula, Ligon Marianne Morris, Diez-Rivero Carmen María, García-Ayuso Diego, Mohanty Soumitra, Viñuela Marcos, Real-Arévalo Irene, Conejero Laura, Brauner Annelie, Subiza José Luis, Mysorekar Indira Uppugunduri
Inmunotek S.L., 28805 Madrid, Spain.
Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Vaccines (Basel). 2024 May 14;12(5):535. doi: 10.3390/vaccines12050535.
MV140 is an inactivated whole-cell bacterial mucosal vaccine with proven clinical efficacy against recurrent urinary tract infections (UTIs). These infections are primarily caused by uropathogenic (UPEC) strains, which are unique in their virulence factors and remarkably diverse. MV140 contains a non-UPEC strain, suggesting that it may induce an immune response against different UPEC-induced UTIs in patients. To verify this, we experimentally evaluated the cellular and humoral responses to UTI89, a prototypical UPEC strain, in mice vaccinated with MV140, as well as the degree of protection achieved in a UPEC UTI89 model of acute cystitis. The results show that both cellular (Th1/Th17) and antibody (IgG/IgA) responses to UTI89 were induced in MV140-immunized mice. MV140 vaccination resulted in an early increased clearance of UTI89 viable bacteria in the bladder and urine following transurethral infection. This was accompanied by a highly significant increase in CD4 T cells in the bladder and an increase in urinary neutrophils. Collectively, our results support that MV140 induces cross-reactive humoral and cellular immune responses and cross-protection against UPEC strains.
MV140是一种灭活全细胞细菌黏膜疫苗，已被证明对复发性尿路感染（UTI）具有临床疗效。这些感染主要由尿路致病性大肠杆菌（UPEC）菌株引起，这些菌株的毒力因子独特且种类繁多。MV140包含一种非UPEC菌株，这表明它可能在患者中诱导针对不同UPEC引起的UTI的免疫反应。为了验证这一点，我们通过实验评估了用MV140免疫的小鼠对典型UPEC菌株UTI89的细胞和体液反应，以及在UPEC UTI89急性膀胱炎模型中实现的保护程度。结果表明，MV140免疫的小鼠对UTI89诱导了细胞（Th1/Th17）和抗体（IgG/IgA）反应。经尿道感染后，MV140疫苗接种导致膀胱和尿液中UTI89活菌的清除率早期增加。这伴随着膀胱中CD4 T细胞的高度显著增加和尿中性粒细胞的增加。总的来说，我们的结果支持MV140诱导交叉反应性体液和细胞免疫反应以及对UPEC菌株的交叉保护。
