title: The 16MΔvjbR as an ideal live attenuated vaccine candidate for differentiation between Brucella vaccination and infection.
abstract: Brucellosis brings great economic burdens for developing countries. Live attenuated vaccines are the most efficient means for prevention and control of animal Brucellosis. However, the difficulties of differentiating of infection from vaccine immunization, which is essential for eradication programs, limit their applications. Therefore, the development of a vaccine that could differentiate infection from immunization will overcome the limitations and get extensive application. VjbR is a quorum sensing regulator involving in Brucella's intracellular survival. The vjbR∷Tn5 mutants have been proven effective against wild type strain challenge, implying its possibility of use in vaccine candidate development. To further evaluate this candidate gene, in the present study, the antigenicity of purified recombinant VjbR protein was analyzed. Antibodies to Brucella melitensis VjbR could be detected in sera from patients and animals with brucellosis but not in control ones, implying the potential use of this protein as a diagnostic antigen. Then a vjbR mutant of B. melitensis 16M was constructed by replacing the vjbR with kanamycin gene. The mutant showed reduced survival in macrophage and mice. Vaccination of BALB/c mice with 16MΔvjbR conferred significant protective immunity against B. melitensis strain 16M challenges, being equivalent to which induced by the license vaccine Rev.1. The vjbR deletion mutant elicited an anti-Brucella-specific immunoglobulin G response and induced the secretion of gamma interferon and interleukin-10. The most importance is that, the use of vjbR mutants as vaccines in association with diagnostic tests based on the VjbR antigen would allow the serological differentiation between infected and vaccinated animals. These results suggest that 16MΔvjbR is an ideal live attenuated vaccine candidate against B. melitensis and deserves further evaluation for vaccine development.
authors.affiliation: Department of Infectious Disease, Institute of Disease Control and Prevention, Academy of Military Medical Science, Beijing 100071, PR China.
authors.forename: Yufei
authors.initials: Y
authors.lastname: Wang
authors.forename: Yaoxia
authors.initials: Y
authors.lastname: Bai
authors.forename: Qing
authors.initials: Q
authors.lastname: Qu
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.forename: Yanfen
authors.initials: Y
authors.lastname: Chen
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Zhong
authors.forename: Yefeng
authors.initials: Y
authors.lastname: Qiu
authors.forename: Tongkun
authors.initials: T
authors.lastname: Wang
authors.forename: Xinying
authors.initials: X
authors.lastname: Du
authors.forename: Zhoujia
authors.initials: Z
authors.lastname: Wang
authors.forename: Shuang
authors.initials: S
authors.lastname: Yu
authors.forename: Simei
authors.initials: S
authors.lastname: Fu
authors.forename: Jing
authors.initials: J
authors.lastname: Yuan
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhen
authors.forename: Yaqing
authors.initials: Y
authors.lastname: Yu
authors.forename: Zeliang
authors.initials: Z
authors.lastname: Chen
authors.forename: Liuyu
authors.initials: L
authors.lastname: Huang
mesh_terms: D000818:Animals; D000917:Antibody Formation; D001426:Bacterial Proteins / Q000097:blood / Q000235:genetics / Q000276:immunology*; D002004:Brucella Vaccine / Q000235:genetics / Q000276:immunology*; D017347:Brucella melitensis / Q000235:genetics / Q000276:immunology*; D002006:Brucellosis / Q000276:immunology / Q000517:prevention & control*; D002460:Cell Line; D005260:Female; D017353:Gene Deletion; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D017384:Sequence Deletion; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology
chemical_list: D001426:Bacterial Proteins; D002004:Brucella Vaccine; D007074:Immunoglobulin G; D014613:Vaccines, Attenuated; D016753:Interleukin-10; D007371:Interferon-gamma