title: Immunization with 3-oxododecanoyl-L-homoserine lactone-r-PcrV conjugate enhances survival of mice against lethal burn infections caused by Pseudomonas aeruginosa.
abstract: Quorum Sensing and type III secretion system play an important role in the virulence of Pseudomonas (P.) aeruginosa in burn wound infections. We aimed to explore the feasibility of using 3-oxo-C₁₂-HSL-r-PcrV conjugate as a candidate vaccine against P. aeruginosa caused infections. 3-oxo-C₁₂-HSL-r-PcrV conjugate was prepared and used for immunization of mice (10 μg, subcutaneous, three times, at 2-week intervals). Mice were divided into five groups: I: PcrV; II: 3-oxo-C₁₂-HSL-r-PcrV (10 μg); III: 3-oxo-C₁₂-HSL-r-PcrV (20 μg); IV: 3-oxo-C₁₂-HSL; and V: PBS receiving groups. After each shot of immunization, total and isotype antibody responses against corresponding antigen were measured to determine the immunization efficacy. One month after the last immunization, all groups were burned and challenged subeschar with P. aeruginosa PAO1. Survival rate and bacterial quantity in the skin and internal organs (liver and spleen) were evaluated 25-hr after burn infection. Immunization with 3-oxo-C₁₂-HSL-r-PcrV significantly increased total IgG and specific subclass antibodies (IgG₁, IgG₂a, IgG₂b, and IgM) in the serum of the groups II and III compared to the control group (p<0.001). While all the control mice (PBS injected group) died within 2 days after bacterial challenge, 64% of the group I, 78% of group II, and 86% of group III, survived within 14 days after challenge. Interestingly, bacterial burden in the liver and spleen of 3-oxo-C₁₂-HSL-r-PcrV injected group (III) was significantly lower than the control group (p<0.001). The present study proposed two-component vaccine to inhibit Pseudomonas infections in burned mouse.
authors.affiliation: Department of Biology, Science and Research branch, Islamic Azad University, Tehran, Iran. id_golpasha@yahoo.com.
authors.forename: Isar Dejban
authors.initials: ID
authors.lastname: Golpasha
authors.forename: Seyed Fazlollah
authors.initials: SF
authors.lastname: Mousavi
authors.forename: Parviz
authors.initials: P
authors.lastname: Owlia
authors.forename: Seyed Davar
authors.initials: SD
authors.lastname: Siadat
authors.forename: Shiva
authors.initials: S
authors.lastname: Irani
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000907:Antibodies, Bacterial / Q000378:metabolism; D000942:Antigens, Bacterial / Q000494:pharmacology / Q000627:therapeutic use*; D001427:Bacterial Toxins / Q000494:pharmacology / Q000627:therapeutic use*; D002056:Burns / Q000382:microbiology*; D004195:Disease Models, Animal; D005260:Female; D006714:Homoserine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D056724:Immunity, Humoral / Q000187:drug effects / Q000276:immunology; D007114:Immunization / Q000379:methods*; D008099:Liver / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D052899:Pore Forming Cytotoxic Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D011552:Pseudomonas Infections / Q000276:immunology / Q000401:mortality* / Q000517:prevention & control*; D011550:Pseudomonas aeruginosa / Q000276:immunology / Q000302:isolation & purification; D012867:Skin / Q000382:microbiology; D013154:Spleen / Q000382:microbiology; D015996:Survival Rate; D018074:Vaccines, Conjugate / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; C109860:N-(3-oxododecanoyl)homoserine lactone; D052899:Pore Forming Cytotoxic Proteins; D018074:Vaccines, Conjugate; C118546:antigen V, Pseudomonas; D006714:Homoserine; D015107:4-Butyrolactone