Abkar Morteza, Lotfi Abbas Sahebghadam, Amani Jafar, Eskandari Khadijeh, Ramandi Mehdi Fasihi, Salimian Jafar, Brujeni Gholamreza Nikbakht, Alamian Saeed, Kamali Mehdi, Koushki Hamid
Department of Molecular Genetics, Faculty of Basic Sciences, Tarbiat Modarres University, Tehran, Iran.
Department of Clinical Biochemistry, Faculty of Medicine, Tarbiat Modares University, P.O. Box: 14155-6343, Tehran, Iran.
Vet Res Commun. 2015 Dec;39(4):217-28. doi: 10.1007/s11259-015-9645-2. Epub 2015 Sep 22.
Brucellosis is the most common zoonotic bacterial disease. Prevention of human brucellosis is achieved through pasteurization of dairy products, appropriate sanitation and vaccination of domestic animals against the Brucella species. B. abortus unlipidated 19 kDa outer membrane protein (U-Omp19) is a promising candidate for a subunit vaccine against brucellosis. This study investigates immunogenicity of Omp19 alone and with Freund's adjuvant (Omp19-IFA) and N-trimethyl chitosan (TMC/Omp19) nanoparticles, as well as the effect of Omp19 administration route on immunological responses and protection. The omp19 gene was expressed in E. coli BL21 (DE3). After purification, the recombinant Omp19 was loaded onto TMC nanoparticles by ionic gelation with tripolyphosphate. Particle size and loading efficiency of the nanoparticles were determined. Omp19-IFA was administered intraperitoneally while TMC/Omp19 nanoparticles were administered orally and intraperitoneally. The results indicated that intraperitoneal (i.p.) immunization by Omp19-IFA and TMC/Omp19 nanoparticles induced Th1 and Th2 immune responses, respectively, whereas oral immunization of TMC/Omp19 nanoparticles induced a mixed Th1/Th17 immune response. Moreover, oral immunization increased IgA levels in feces. Immunized mice were challenged with virulent B. melitensis 16 M and B. abortus 544. Oral immunization with TMC/Omp19 nanoparticles induced a remarkably high protection level against B. melitensis and B. abortus. The results showed that immunization route has a pivotal role in immune response polarization and protective efficiency of Omp19 antigen. Also, it was deduced that the higher protection level achieved through oral administration of TMC/Omp19 nanoparticles may be due to the elicited Th17 response.
布鲁氏菌病是最常见的人畜共患细菌性疾病。通过对乳制品进行巴氏消毒、采取适当的卫生措施以及对家畜接种针对布鲁氏菌属的疫苗来预防人类布鲁氏菌病。流产布鲁氏菌未脂化的19 kDa外膜蛋白(U-Omp19)是一种很有前景的布鲁氏菌病亚单位疫苗候选物。本研究调查了单独的Omp19以及与弗氏佐剂(Omp19-IFA)和N-三甲基壳聚糖(TMC/Omp19)纳米颗粒联合使用时的免疫原性,以及Omp19给药途径对免疫反应和保护作用的影响。omp19基因在大肠杆菌BL21(DE3)中表达。纯化后,通过与三聚磷酸进行离子凝胶化将重组Omp19负载到TMC纳米颗粒上。测定了纳米颗粒的粒径和负载效率。Omp19-IFA通过腹腔注射给药,而TMC/Omp19纳米颗粒通过口服和腹腔注射给药。结果表明,Omp19-IFA和TMC/Omp19纳米颗粒腹腔内免疫分别诱导Th1和Th2免疫反应,而TMC/Omp19纳米颗粒口服免疫诱导混合的Th1/Th17免疫反应。此外,口服免疫增加了粪便中的IgA水平。用强毒力的羊种布鲁氏菌16 M和流产布鲁氏菌544对免疫小鼠进行攻毒。用TMC/Omp19纳米颗粒口服免疫诱导了对羊种布鲁氏菌和流产布鲁氏菌的显著高保护水平。结果表明,给药途径在Omp19抗原的免疫反应极化和保护效率中起关键作用。此外,推断通过口服TMC/Omp19纳米颗粒获得的较高保护水平可能归因于引发的Th17反应。