Multivalent DNA vaccine protects mice against pulmonary infection caused by Pseudomonas aeruginosa.
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.
Saha
Sukumar
S
Department of Molecular Biodefense Research, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
Takeshita
Fumihiko
F
Sasaki
Shin
S
Matsuda
Tomoko
T
Tanaka
Toshiyuki
T
Tozuka
Miyuki
M
Takase
Keiko
K
Matsumoto
Tetsuya
T
Okuda
Katsuji
K
Ishii
Norihisa
N
Yamaguchi
Keizo
K
Klinman
Dennis M
DM
Xin
Ke-Qin
KQ
Okuda
Kenji
K
D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology; D001427:Bacterial Toxins / Q000235:genetics / Q000276:immunology; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D019470:Biolistics / Q000379:methods; D018893:Bronchoalveolar Lavage / Q000379:methods; D054426:Chemokine CXCL2; D018925:Chemokines / Q000276:immunology; D018274:Electroporation / Q000379:methods; D005260:Female; D036781:Fimbriae Proteins / Q000235:genetics / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007371:Interferon-gamma; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000235:genetics; D018410:Pneumonia, Bacterial / Q000276:immunology / Q000517:prevention & control*; D052899:Pore Forming Cytotoxic Proteins; D011552:Pseudomonas Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D001428:Bacterial Vaccines; D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D007074:Immunoglobulin G; D052899:Pore Forming Cytotoxic Proteins; D019444:Vaccines, DNA; C118546:antigen V, Pseudomonas; D036781:Fimbriae Proteins; D007371:Interferon-gamma