Protective effects of affinity-purified antibody and truncated vaccines against Pseudomonas aeruginosa V-antigen in neutropenic mice.
Virulent P. aeruginosa strains express PcrV, one of the translocational components of the type III secretion system. PcrV has been reported to be a protective antigen against lethal P. aeruginosa infection. The PcrV region, which contributes to protective immunity against P. aeruginosa infection, was investigated by using genetically engineered, truncated PcrV proteins and affinity-purified anti-PcrV antibodies against the truncated PcrV proteins. The efficacy of active and passive immunization against PcrV was tested in mice with cyclophosphamide-induced immunosuppression by intraabdominal challenge of P. aeruginosa. Active immunization with either full-length PcrV1-294 or PcrV139-294 significantly improved the survival of mice infected with P. aeruginosa, while PcrV139-258, PcrV139-234, PcrV197-294, and PcrV261-294 were not protective. These results suggest that an effective PcrV vaccine needs to contain not only the Mab166 epitope (PcrV144-257) but also the carboxyl terminal tail of PcrV. In the case of passive immunization, administration of affinity-purified anti-PcrV IgG against either PcrV1-294 or PcrV139-258 showed significantly higher efficacy against lethal P. aeruginosa infection than did original anti-PcrV IgG and Mab166. The increased efficacy of affinity-purified anti-PcrV IgG implies that more potent anti-PcrV strategies are possible. The results of this study are crucial to the development of an effective PcrV vaccine for active immunization and to an appropriate blocking anti-PcrV antibody against P. aeruginosa infection in humans.
Moriyama
Kiyoshi
K
Department of Anesthesia, University of California San Francisco, San Francisco, California 94143, USA. mokiyokeio@gmail.com
Wiener-Kronish
Jeanine P
JP
Sawa
Teiji
T
D000818:Animals; D000907:Antibodies, Bacterial / Q000008:administration & dosage* / Q000276:immunology / Q000302:isolation & purification; D000915:Antibody Affinity / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology*; D001427:Bacterial Toxins / Q000276:immunology*; D003520:Cyclophosphamide; D007116:Immunization, Passive; D007165:Immunosuppression Therapy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009503:Neutropenia / Q000276:immunology; D052899:Pore Forming Cytotoxic Proteins / Q000276:immunology*; D011552:Pseudomonas Infections / Q000276:immunology / Q000517:prevention & control*; D054406:Pseudomonas Vaccines / Q000276:immunology*; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D052899:Pore Forming Cytotoxic Proteins; D054406:Pseudomonas Vaccines; D014614:Vaccines, Synthetic; C118546:antigen V, Pseudomonas; D003520:Cyclophosphamide