Department of Microbiology and Immunology, Faculty of Pharmacy, Mansoura University, Egypt.
Department of Microbiology and Immunology, Faculty of Pharmacy, Mansoura University, Egypt; Faculty of Pharmacy, Northern Border University, Rafha, Saudi Arabia.
J Microbiol Immunol Infect. 2018 Jun;51(3):312-320. doi: 10.1016/j.jmii.2016.08.014. Epub 2017 Feb 20.
Pseudomonas aeruginosa is a Gram-negative opportunistic bacterium, which considered as a common cause of nosocomial infection and life-threatening complications in immunocompromized and cystic fibrosis patients. Here, we evaluate the protective effect of recombinant vaccines composed of outer membrane proteins OprF and OprI alone or in combination with flagellin B against mucoid and nonmucoid pseudomonas infection.
BALB/C mice were immunized subcutaneous using OprF and OprI with or without flagellin B and antibody titers were determined. Serum bactericidal and opsonophagocytosis activities of immunized and control sera were estimated against mucoid and nonmucoid pseudomonas strains. Lung tissue sections from immunized and nonimmunized mice were analyzed and the levels of peripheral neutrophils infiltration into the lung and tissue inflammation were scored.
Subcutaneous immunization using OprF and OprI with or without flagellin B elicited higher antibody titers against OprF, OprI, and flagellin B. The produced antibodies successfully opsonized both mucoid and nonmucoid strains with subsequent activation of the terminal pathway of complement that enhances killing of nonmucoid strains via complement-mediated lysis. Furthermore, opsonized mucoid and nonmucoid strains showed enhanced opsonophagocytosis via human peripheral neutrophils, a mechanism that kills P. aeruginosa when complement mediated lysis is not effective especially with mucoid strains. Immunized mice also showed a significant prolonged survival time, lower bacteremia, and reduced lung damage when compared with control nonimmunized mice.
Our data showed that mice immunized with OprF/OprI or OprF/OprI and flagellin B are significantly protected from infection caused by mucoid and nonmucoid strains of P. aeruginosa.
铜绿假单胞菌是一种革兰氏阴性机会致病菌,被认为是免疫功能低下和囊性纤维化患者医院感染和危及生命并发症的常见原因。在这里,我们评估了由外膜蛋白 OprF 和 OprI 单独或与鞭毛蛋白 B 组合组成的重组疫苗对粘液型和非粘液型铜绿假单胞菌感染的保护作用。
BALB/C 小鼠通过皮下免疫 OprF 和 OprI 加或不加鞭毛蛋白 B,并测定抗体滴度。用免疫和对照血清估计针对粘液型和非粘液型铜绿假单胞菌菌株的血清杀菌和调理吞噬作用。分析免疫和非免疫小鼠的肺组织切片,并对肺组织中外周中性粒细胞浸润和组织炎症的水平进行评分。
皮下免疫 OprF 和 OprI 加或不加鞭毛蛋白 B 可引起针对 OprF、OprI 和鞭毛蛋白 B 的更高抗体滴度。产生的抗体成功调理了粘液型和非粘液型菌株,随后激活补体的终末途径,增强了补体介导的裂解对非粘液型菌株的杀伤。此外,调理后的粘液型和非粘液型菌株通过人外周中性粒细胞表现出增强的调理吞噬作用,当补体介导的裂解无效时,特别是对于粘液型菌株,这种机制可杀死铜绿假单胞菌。与对照非免疫小鼠相比,免疫小鼠的存活时间显著延长,菌血症减少,肺损伤减轻。
我们的数据表明,用 OprF/OprI 或 OprF/OprI 和鞭毛蛋白 B 免疫的小鼠对粘液型和非粘液型铜绿假单胞菌菌株引起的感染有显著的保护作用。