Al-Mariri A, Tibor A, Mertens P, De Bolle X, Michel P, Godfroid J, Walravens K, Letesson J J
Unité de Recherche en Biologie Moléculaire, Laboratoire d'Immunologie et de Microbiologie, Facultés Universitaires Notre-Dame de la Paix, B-5000 Namur, Belgium.
Infect Immun. 2001 Oct;69(10):6264-70. doi: 10.1128/IAI.69.10.6264-6270.2001.
In this study, we evaluated the ability of DNA vaccines encoding the bacterioferritin (BFR) or P39 proteins of Brucella spp. to induce cellular and humoral immune responses and to protect BALB/c mice against a challenge with B. abortus 544. We constructed eukaryotic expression vectors called pCIBFR and pCIP39, encoding BFR or P39 antigens, respectively, and we verified that these proteins were produced after transfection of COS-7 cells. PCIBFR or pCIP39 was injected intramuscularly three times, at 3-week intervals. pCIP39 induced higher antibody responses than did the DNA vector encoding BFR. Both vectors elicited a T-cell-proliferative response and also induced a strong gamma interferon production upon restimulation with either the specific antigens or Brucella extract. In this report, we also demonstrate that animals immunized with these plasmids elicited a strong and long-lived memory immune response which persisted at least 3 months after the third vaccination. Furthermore, pCIBFR and pCIP39 induced a typical T-helper 1-dominated immune response in mice, as determined by cytokine or immunoglobulin G isotype analysis. The pCIP39 delivered by intramuscular injection (but not the pCIBFR or control vectors) induced a moderate protection in BALB/c mice challenged with B. abortus 544 compared to that observed in positive control mice vaccinated with S19.
在本研究中,我们评估了编码布鲁氏菌属细菌铁蛋白(BFR)或P39蛋白的DNA疫苗诱导细胞免疫和体液免疫应答以及保护BALB/c小鼠抵御流产布鲁氏菌544攻击的能力。我们构建了分别编码BFR或P39抗原的真核表达载体pCIBFR和pCIP39,并验证了这些蛋白在转染COS-7细胞后能够产生。pCIBFR或pCIP39每隔3周进行3次肌肉注射。pCIP39诱导产生的抗体应答高于编码BFR的DNA载体。两种载体均引发T细胞增殖应答,并且在用特异性抗原或布鲁氏菌提取物再次刺激时均诱导产生强烈γ干扰素。在本报告中,我们还证明用这些质粒免疫的动物引发了强烈且持久的记忆免疫应答,该应答在第三次接种后至少持续3个月。此外,通过细胞因子或免疫球蛋白G同种型分析确定,pCIBFR和pCIP39在小鼠中诱导了典型的以辅助性T细胞1为主导的免疫应答。与接种S19的阳性对照小鼠相比,肌肉注射的pCIP39(而非pCIBFR或对照载体)在受到流产布鲁氏菌544攻击的BALB/c小鼠中诱导了适度的保护作用。