Cassataro Juliana, Pasquevich Karina A, Estein Silvia M, Laplagne Diego A, Zwerdling Astrid, de la Barrera Silvia, Bowden Raúl, Fossati Carlos A, Giambartolomei Guillermo H, Goldbaum Fernando A
Laboratorio de Inmunogenética, Hospital de Clínicas José de San Martín, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
Vaccine. 2007 Aug 10;25(32):5958-67. doi: 10.1016/j.vaccine.2007.05.049. Epub 2007 Jun 12.
In the present study, we reported an attempt to improve the immunogenicity and protective capacity of the chimera BLSOmp31 using a different antigen delivery: DNA vaccination. Vaccination of BALB/c mice with the DNA vaccine coding for the chimera BLSOmp31 (pCIBLSOmp31) provided the best protection level against Brucella ovis, which was significantly higher than the given by the co-delivery of both plasmids coding for the whole proteins (pcDNABLS+pCIOmp31) and even higher than the control vaccine Rev.1. Moreover, pCIBLSOmp31 induced higher protection against Brucella melitensis than pcDNABLS+pCIOmp31 but similar protection than Rev.1. The chimera induced a strong humoral response against the inserted peptide. It also induced peptide- and BLS-specific cytotoxic T responses. The insertion of this peptide on BLS induced stronger T helper 1 responses specific for the carrier (BLS), thus our results represent a case of synergic strengthening between two Brucella antigens. Hitherto, this is the first indication that a recombinant subunit vaccine elicits greater protection than whole Brucella.
在本研究中,我们报告了一项尝试,即通过一种不同的抗原递送方式——DNA疫苗接种,来提高嵌合体BLSOmp31的免疫原性和保护能力。用编码嵌合体BLSOmp31的DNA疫苗(pCIBLSOmp31)对BALB/c小鼠进行疫苗接种,提供了针对绵羊布鲁氏菌的最佳保护水平,该水平显著高于编码全蛋白的两种质粒共同递送(pcDNABLS + pCIOmp31)所提供的保护水平,甚至高于对照疫苗Rev.1。此外,pCIBLSOmp31诱导的针对流产布鲁氏菌的保护作用高于pcDNABLS + pCIOmp31,但与Rev.1诱导的保护作用相似。该嵌合体诱导了针对插入肽的强烈体液反应。它还诱导了肽特异性和BLS特异性的细胞毒性T反应。在BLS上插入该肽诱导了更强的针对载体(BLS)的辅助性T细胞1反应,因此我们的结果代表了两种布鲁氏菌抗原之间协同增强的一个例子。迄今为止,这是首次表明重组亚单位疫苗比完整布鲁氏菌疫苗引发更大保护作用的迹象。