Saha Sukumar, Takeshita Fumihiko, Sasaki Shin, Matsuda Tomoko, Tanaka Toshiyuki, Tozuka Miyuki, Takase Keiko, Matsumoto Tetsuya, Okuda Katsuji, Ishii Norihisa, Yamaguchi Keizo, Klinman Dennis M, Xin Ke-Qin, Okuda Kenji
Department of Molecular Biodefense Research, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
Vaccine. 2006 Sep 11;24(37-39):6240-9. doi: 10.1016/j.vaccine.2006.05.077. Epub 2006 Jun 9.
For efficacious vaccine development against Pseudomonas aeruginosa (P. aeruginosa), the immunogenicity of multivalent DNA vaccine was evaluated. Three different plasmids each targeting a fusion of outer membrane proteins (OprF/OprI), a protein regulating type III secretion system (PcrV), or an appendage (PilA) were prepared and mice were immunized with single (monovalent) or a combination of these plasmids (multivalent) via intramuscular electroporation (imEPT) or gene gun. Immunization with multivalent DNA vaccine via imEPT induced the most potent protection against lethal pneumonia. Although the serum levels of IgG binding to whole bacteria cells were comparable between groups, the strongest immune protection was associated with the serum levels of Th1-dominated multivalent IgG, the bronchoalveolar levels of macrophage inflammatory protein 2 (MIP-2) and IFN-gamma, and the number of neutrophils and macrophages in the bronchoalveolar lavage following intranasal challenge. These results implied the possible clinical application of multivalent DNA vaccine against P. aeruginosa.
为了开发针对铜绿假单胞菌的有效疫苗，对多价DNA疫苗的免疫原性进行了评估。制备了三种不同的质粒，分别靶向外膜蛋白融合体（OprF/OprI）、调节III型分泌系统的蛋白（PcrV）或附属物（PilA），并通过肌肉电穿孔（imEPT）或基因枪用单一（单价）或这些质粒的组合（多价）对小鼠进行免疫。通过imEPT接种多价DNA疫苗可诱导对致死性肺炎的最强保护作用。尽管各组之间与全细菌细胞结合的IgG血清水平相当，但最强的免疫保护与Th1主导的多价IgG血清水平、支气管肺泡巨噬细胞炎性蛋白2（MIP-2）和IFN-γ水平以及鼻内攻击后支气管肺泡灌洗中的中性粒细胞和巨噬细胞数量有关。这些结果表明多价DNA疫苗针对铜绿假单胞菌可能具有临床应用价值。
