title: X-ray Irradiated Vaccine Confers protection against Pneumonia caused by Pseudomonas aeruginosa.
abstract: Pseudomonas aeruginosa is a gram-negative bacterium and one of the leading causes of nosocomial infection worldwide, however, no effective vaccine is currently available in the market. Here, we demonstrate that inactivation of the bacteria by X-ray irradiation inhibits its replication capability but retained antigenic expression functionally thus allowing its use as a potential vaccine. Mice immunized by this vaccine were challenged by the parental strain, the O-antigen-homologous strain PAO-1 (O2/O5) and heterologous strain PAO-6 (O6) in an acute pneumonia model. We further measured the protective effect of the vaccine, as well as host innate and cellular immunity responses. We found immunized mice could protect against both strains. Notably, the antiserum only had significant protective role against similar bacteria, while adoptive transfer of lymphocytes significantly controlled the spread of the virulent heterologous serogroup PAO-6 infection, and the protective role could be reversed by CD4 rather than CD8 antibody. We further revealed that vaccinated mice could rapidly recruit neutrophils to the airways early after intranasal challenge by PAO-6, and the irradiated vaccine was proved to be protective by the generated CD4(+) IL-17(+) Th17 cells. In conclusion, the generation of inactivated but metabolically active microbes is a promising strategy for safely vaccinating against Pseudomonas aeruginosa.
authors.affiliation: Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.|State Key Labortary of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Cheng Du, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Labortary of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Cheng Du, China.
authors.forename: Zhenling
authors.initials: Z
authors.lastname: Wang
authors.affiliation: State Key Labortary of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Cheng Du, China.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Liu
authors.affiliation: State Key Labortary of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Cheng Du, China.
authors.forename: Jianying
authors.initials: J
authors.lastname: Tang
authors.affiliation: State Key Labortary of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Cheng Du, China.|Department of Oncology, Third Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Peng
authors.affiliation: State Key Labortary of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Cheng Du, China.
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Wei
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D058491:Bacterial Load; D001428:Bacterial Vaccines / Q000276:immunology* / Q000528:radiation effects; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D004195:Disease Models, Animal; D005260:Female; D007114:Immunization; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D050296:Microbial Viability / Q000276:immunology; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D011552:Pseudomonas Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D011550:Pseudomonas aeruginosa / Q000276:immunology* / Q000378:metabolism / Q000528:radiation effects*; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism; D015164:Vaccines, Inactivated / Q000276:immunology* / Q000528:radiation effects; D014965:X-Rays
chemical_list: D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D008070:Lipopolysaccharides; D015164:Vaccines, Inactivated