Frontiers in Biology

, Volume 8, Issue 1, pp 60–77 | Cite as

Progress in Brucella vaccine development

  • Xinghong YangEmail author
  • Jerod A. Skyberg
  • Ling Cao
  • Beata Clapp
  • Theresa Thornburg
  • David W. Pascual


Brucella spp. are zoonotic, facultative intracellular pathogens, which cause animal and human disease. Animal disease results in abortion of fetuses; in humans, it manifests flu-like symptoms with an undulant fever, with osteoarthritis as a common complication of infection. Antibiotic regimens for human brucellosis patients may last several months and are not always completely effective. While there are no vaccines for humans, several licensed live Brucella vaccines are available for use in livestock. The performance of these animal vaccines is dependent upon the host species, dose, and route of immunization. Newly engineered live vaccines, lacking well-defined virulence factors, retain low residual virulence, are highly protective, and may someday replace currently used animal vaccines. These also have possible human applications. Moreover, due to their enhanced safety and efficacy in animal models, subunit vaccines for brucellosis show great promise for their application in livestock and humans. This review summarizes the progress of brucellosis vaccine development and presents an overview of candidate vaccines.


Brucella brucellosis zoonosis livestock vaccines 


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  1. Abu Shaqra Q M (2000). Epidemiological aspects of brucellosis in Jordan. Eur J Epidemiol, 16(6): 581–584PubMedCrossRefGoogle Scholar
  2. Adone R, Ciuchini F, Marianelli C, Tarantino M, Pistoia C, Marcon G, Petrucci P, Francia M, Riccardi G, Pasquali P (2005). Protective properties of rifampin-resistant rough mutants of Brucella melitensis. Infect Immun, 73(7): 4198–4204PubMedCrossRefGoogle Scholar
  3. Al-Mariri A, Tibor A, Mertens P, De Bolle X, Michel P, Godefroid J, Walravens K, Letesson J J (2001). Protection of BALB/c mice against Brucella abortus 544 challenge by vaccination with bacterioferritin or P39 recombinant proteins with CpG oligodeoxynucleotides as adjuvant. Infect Immun, 69(8): 4816–4822PubMedCrossRefGoogle Scholar
  4. Alcantara R B, Read R D, Valderas M W, Brown T D, Roop R M 2nd (2004). Intact purine biosynthesis pathways are required for wildtype virulence of Brucella abortus 2308 in the BALB/c mouse model. Infect Immun, 72(8): 4911–4917PubMedCrossRefGoogle Scholar
  5. Almirón M, Martínez M, Sanjuan N, Ugalde R A (2001). Ferrochelatase is present in Brucella abortus and is critical for its intracellular survival and virulence. Infect Immun, 69(10): 6225–6230PubMedCrossRefGoogle Scholar
  6. Alton G G (1966). Duration of the immunity produced in goats by the Rev. 1 Brucella melitensis vaccine. J Comp Pathol, 76(3): 241–253PubMedCrossRefGoogle Scholar
  7. Alton G G (1968). Further studies on the duration of the immunity produced in goats by the Rev. 1 Brucella melitensis vaccine. J Comp Pathol, 78(2): 173–178PubMedCrossRefGoogle Scholar
  8. Arellano-Reynoso B, Lapaque N, Salcedo S, Briones G, Ciocchini A E, Ugalde R, Moreno E, Moriyón I, Gorvel J P (2005). Cyclic β-1,2-glucan is a Brucella virulence factor required for intracellular survival. Nat Immunol, 6(6): 618–625PubMedCrossRefGoogle Scholar
  9. Arenas-Gamboa AM, Ficht T A, Davis D S, Elzer P H, Kahl-McDonagh M, Wong-Gonzalez A, Rice-Ficht A C (2009a). Oral vaccination with microencapsuled strain 19 vaccine confers enhanced protection against Brucella abortus strain 2308 challenge in red deer (Cervus elaphus elaphus). J Wildl Dis, 45(4): 1021–1029PubMedGoogle Scholar
  10. Arenas-Gamboa A M, Ficht T A, Davis D S, Elzer P H, Wong-Gonzalez A, Rice-Ficht A C (2009b). Enhanced immune response of red deer (Cervus elaphus) to live rb51 vaccine strain using composite microspheres. J Wildl Dis, 45(1): 165–173PubMedGoogle Scholar
  11. Arenas-Gamboa A M, Ficht T A, Kahl-McDonagh M M, Gomez G, Rice-Ficht A C (2009c). The Brucella abortus S19 ΔvjbR live vaccine candidate is safer than S19 and confers protection against wild-type challenge in BALB/c mice when delivered in a sustainedrelease vehicle. Infect Immun, 77(2): 877–884PubMedCrossRefGoogle Scholar
  12. Arenas-Gamboa A M, Ficht T A, Kahl-McDonagh M M, Rice-Ficht A C (2008). Immunization with a single dose of a microencapsulated Brucella melitensis mutant enhances protection against wild-type challenge. Infect Immun, 76(6): 2448–2455PubMedCrossRefGoogle Scholar
  13. Arenas-Gamboa A M, Rice-Ficht A C, Kahl-McDonagh M M, Ficht T A (2011). Protective efficacy and safety of Brucella melitensis 16MΔmucR against intraperitoneal and aerosol challenge in BALB/c mice. Infect Immun, 79(9): 3653–3658PubMedCrossRefGoogle Scholar
  14. Ascón M A, Ochoa-Repáraz J, Walters N, Pascual D W (2005). Partially assembled K99 fimbriae are required for protection. Infect Immun, 73(11): 7274–7280PubMedCrossRefGoogle Scholar
  15. Ashford D A, di Pietra J, Lingappa J, Woods C, Noll H, Neville B, Weyant R, Bragg S L, Spiegel R A, Tappero J, Perkins B A (2004). Adverse events in humans associated with accidental exposure to the livestock brucellosis vaccine RB51. Vaccine, 22(25–26): 3435–3439PubMedCrossRefGoogle Scholar
  16. Atluri V L, Xavier M N, de Jong M F, den Hartigh A B, Tsolis R E (2011). Interactions of the human pathogenic Brucella species with their hosts. Annu Rev Microbiol, 65(1): 523–541PubMedCrossRefGoogle Scholar
  17. Audic S, Lescot M, Claverie J M, Scholz H C (2009). Brucella microti: the genome sequence of an emerging pathogen. BMC Genomics, 10(1): 352PubMedCrossRefGoogle Scholar
  18. Bäckhed F, Normark S, Schweda E K, Oscarson S, Richter-Dahlfors A (2003). Structural requirements for TLR4-mediated LPS signalling: a biological role for LPS modifications. Microbes Infect, 5(12): 1057–1063PubMedCrossRefGoogle Scholar
  19. Baldi P C, Wallach J C, Ferrero M C, Delpino M V, and Fossati C A (2008). Occupational infection due to Brucella abortus S19 among workers involved in vaccine production in Argentina. CMI, 14: 805–807PubMedGoogle Scholar
  20. Baloglu S, Boyle S M, Vemulapalli R, Sriranganathan N, Schurig G G, Toth T E (2005). Immune responses of mice to vaccinia virus recombinants expressing either Listeria monocytogenes partial listeriolysin or Brucella abortus ribosomal L7/L12 protein. Vet Microbiol, 109(1–2): 11–17PubMedCrossRefGoogle Scholar
  21. Banai M (2002). Control of small ruminant brucellosis by use of Brucella melitensis Rev.1 vaccine: laboratory aspects and field observations. Vet Microbiol, 90(1–4): 497–519PubMedCrossRefGoogle Scholar
  22. Bandara A B, Poff-Reichow S A, Nikolich M, Hoover D L, Sriranganathan N, Schurig G G, Dobrean V, Boyle S M (2009). Simultaneous expression of homologous and heterologous antigens in rough, attenuated Brucella melitensis. Microbes Infect, 11(3): 424–428PubMedCrossRefGoogle Scholar
  23. Barquero-Calvo E, Chaves-Olarte E, Weiss D S, Guzmán-Verri C, Chacón-Díaz C, Rucavado A, Moriyón I, Moreno E (2007). Brucella abortus uses a stealthy strategy to avoid activation of the innate immune system during the onset of infection. PLoS ONE, 2(7): e631PubMedCrossRefGoogle Scholar
  24. Barrio M B, Grilló M J, Muñoz P M, Jacques I, González D, de Miguel M J, Marín C M, Barberán M, Letesson J J, Gorvel J P, Moriyón I, Blasco J M, Zygmunt M S (2009). Rough mutants defective in core and O-polysaccharide synthesis and export induce antibodies reacting in an indirect ELISA with smooth lipopolysaccharide and are less effective than Rev 1 vaccine against Brucella melitensis infection of sheep. Vaccine, 27(11): 1741–1749PubMedCrossRefGoogle Scholar
  25. Barrionuevo P, Delpino MV, Velásquez L N, García Samartino C, Coria L M, Ibañez A E, Rodríguez M E, Cassataro J, Giambartolomei G H (2011). Brucella abortus inhibits IFN-γ-induced FcγRI expression and FcγRI-restricted phagocytosis via toll-like receptor 2 on human monocytes/macrophages. Microbes Infect, 13(3): 239–250PubMedCrossRefGoogle Scholar
  26. Beckett F W, MacDiarmid S C (1985). The effect of reduced-dose Brucella abortus strain 19 vaccination in accredited dairy herds. Br Vet J, 141(5): 507–514PubMedCrossRefGoogle Scholar
  27. Bercovich Z (2000). The use of skin delayed-type hypersensitivity as an adjunct test to diagnose brucellosis in cattle: a review. Vet Q, 22(3): 123–130PubMedCrossRefGoogle Scholar
  28. Bhattacharjee A K, Izadjoo M J, Zollinger W D, Nikolich M P, Hoover D L (2006). Comparison of protective efficacy of subcutaneous versus intranasal immunization of mice with a Brucella melitensis lipopolysaccharide subunit vaccine. Infect Immun, 74(10): 5820–5825PubMedCrossRefGoogle Scholar
  29. Blasco J M, Díaz R (1993). Brucella melitensis Rev-1 vaccine as a cause of human brucellosis. Lancet, 342(8874): 805PubMedCrossRefGoogle Scholar
  30. Blasco J M, Marín C, Jiménez de Bagüés M P, Barberán M (1993). Efficacy of Brucella suis strain 2 vaccine against Brucella ovis in rams. Vaccine, 11(13): 1291–1294PubMedCrossRefGoogle Scholar
  31. Borts I H, McNutt S H, Jordan C F (1946). Brucella melitensis isolated from swine tissues in Iowa. J Am Med Assoc, 130(14): 966–966PubMedGoogle Scholar
  32. Boschiroli M L, Cravero S L, Arese A I, Campos E, Rossetti O L (1997). Protection against infection in mice vaccinated with a Brucella abortus mutant. Infect Immun, 65(2): 798–800PubMedGoogle Scholar
  33. Bosseray N (1991). Brucella melitensis Rev. 1 living attenuated vaccine: stability of markers, residual virulence and immunogenicity in mice. Biologicals, 19(4): 355–363PubMedCrossRefGoogle Scholar
  34. Bosseray N, Plommet M (1990). Brucella suis S2, brucella melitensis Rev. 1 and Brucella abortus S19 living vaccines: residual virulence and immunity induced against three Brucella species challenge strains in mice. Vaccine, 8(5): 462–468PubMedCrossRefGoogle Scholar
  35. Briones G, Iñón de Iannino N, Roset M, Vigliocco A, Paulo P S, Ugalde R A (2001). Brucella abortus cyclic beta-1,2-glucan mutants have reduced virulence in mice and are defective in intracellular replication in HeLa cells. Infect Immun, 69(7): 4528–4535PubMedCrossRefGoogle Scholar
  36. Burkhardt S, Jiménez de Bagüés M P, Liautard J P, Köhler S (2005). Analysis of the behavior of eryC mutants of Brucella suis attenuated in macrophages. Infect Immun, 73(10): 6782–6790PubMedCrossRefGoogle Scholar
  37. Buyukcangaz E, Sen A (2007). The first isolation of Brucella melitensis from bovine aborted fetus in Turkey. J Biol Environ Sci, 1: 139–142Google Scholar
  38. Cabrera A, Sáez D, Céspedes S, Andrews E, Oñate A (2009). Vaccination with recombinant Semliki Forest virus particles expressing translation initiation factor 3 of Brucella abortus induces protective immunity in BALB/c mice. Immunobiology, 214(6): 467–474PubMedCrossRefGoogle Scholar
  39. Caporale V, Bonfini B, Di Giannatale E, Di Provvido A, Forcella S, Giovannini A, Tittarelli M, Scacchia M (2010). Efficacy of Brucella abortus vaccine strain RB51 compared to the reference vaccine Brucella abortus strain 19 in water buffalo. Vet Ital, 46(1): 13–19PubMedGoogle Scholar
  40. Cardena A P, Herrera D M, Zamora J L F, Pina F B, Sanchez B M, Ruiz E J G, Williams J J, Alvarez F M, Castro R F (2009). Evaluation of vaccination with Brucella abortus S19 vaccine in cattle naturally infected with brucellosis in productive systems found in the Mexican Tropic. Int J Dairy Sci, 4(4): 142–151CrossRefGoogle Scholar
  41. Cassataro J, Estein S M, Pasquevich K A, Velikovsky C A, de la Barrera S, Bowden R, Fossati C A, Giambartolomei G H (2005). Vaccination with the recombinant Brucella outer membrane protein 31 or a derived 27-amino-acid synthetic peptide elicits a CD4+ T helper 1 response that protects against Brucella melitensis infection. Infect Immun, 73(12): 8079–8088PubMedCrossRefGoogle Scholar
  42. Castaño M J, Solera J (2009). Chronic brucellosis and persistence of Brucella melitensis DNA. J Clin Microbiol, 47(7): 2084–2089PubMedCrossRefGoogle Scholar
  43. Centers for Disease Control and Prevention (CDC) (1998). Human exposure to Brucella abortus strain RB51—Kansas, 1997. MMWR Morb Mortal Wkly Rep, 47(9): 172–175Google Scholar
  44. Cespedes S, Andrews E, Folch H, Oñate A (2000). Identification and partial characterisation of a new protective antigen of Brucella abortus. J Med Microbiol, 49(2): 165–170PubMedGoogle Scholar
  45. Chacón-Díaz C, Muñoz-Rodríguez M, Barquero-Calvo E, Guzmán-Verri C, Chaves-Olarte E, Grilló M J, Moreno E (2011). The use of green fluorescent protein as a marker for Brucella vaccines. Vaccine, 29(3): 577–582PubMedCrossRefGoogle Scholar
  46. Chain P S, Comerci D J, Tolmasky M E, Larimer F W, Malfatti S A, Vergez L M, Aguero F, Land M L, Ugalde R A, Garcia E (2005). Whole-genome analyses of speciation events in pathogenic Brucellae. Infect Immun, 73(12): 8353–8361PubMedCrossRefGoogle Scholar
  47. Cheville N F, McCullough D R, Paulson L R (1998). Brucellosis in the greater Yellowstone area, Vol National Research Council (U.S.). Board on Agriculture. National Research Council (U.S.). Board on Environmental Studies and Toxicology, Washington D C, National Academy PressGoogle Scholar
  48. Cheville N F, Olsen S C, Jensen A E, Stevens M G, Florance A M, Houng H S, Drazek E S, Warren R L, Hadfield T L, Hoover D L (1996a). Bacterial persistence and immunity in goats vaccinated with a purE deletion mutant or the parental 16M strain of Brucella melitensis. Infect Immun, 64(7): 2431–2439PubMedGoogle Scholar
  49. Cheville N F, Olsen S C, Jensen A E, Stevens M G, Palmer M V, Florance A M (1996b). Effects of age at vaccination on efficacy of Brucella abortus strain RB51 to protect cattle against brucellosis. Am J Vet Res, 57(8): 1153–1156PubMedGoogle Scholar
  50. Cheville N F, Stevens M G, Jensen A E, Tatum F M, Halling S M (1993). Immune responses and protection against infection and abortion in cattle experimentally vaccinated with mutant strains of Brucella abortus. Am J Vet Res, 54(10): 1591–1597PubMedGoogle Scholar
  51. Clapp B, Skyberg J A, Yang X, Thornburg T, Walters N, Pascual D W (2011a). Protective live oral brucellosis vaccines stimulate Th1 and th17 cell responses. Infect Immun, 79(10): 4165–4174PubMedCrossRefGoogle Scholar
  52. Clapp B, Walters N, Thornburg T, Hoyt T, Yang X, Pascual D W (2011b). DNA vaccination of bison to brucellar antigens elicits elevated antibody and IFN-γ responses. J Wildl Dis, 47(3): 501–510PubMedGoogle Scholar
  53. Cloeckaert A, Debbarh H S, Vizcaíno N, Saman E, Dubray G, Zygmunt M S (1996). Cloning, nucleotide sequence, and expression of the Brucella melitensis bp26 gene coding for a protein immunogenic in infected sheep. FEMS Microbiol Lett, 140(2–3): 139–144PubMedCrossRefGoogle Scholar
  54. Commander N J, Spencer S A, Wren B W, MacMillan A P (2007). The identification of two protective DNA vaccines from a panel of five plasmid constructs encoding Brucella melitensis 16M genes. Vaccine, 25(1): 43–54PubMedCrossRefGoogle Scholar
  55. Conde-Alvarez R, Grilló M J, Salcedo S P, de Miguel M J, Fugier E, Gorvel J P, Moriyón I, Iriarte M (2006). Synthesis of phosphatidylcholine, a typical eukaryotic phospholipid, is necessary for full virulence of the intracellular bacterial parasite Brucella abortus. Cell Microbiol, 8(8): 1322–1335PubMedCrossRefGoogle Scholar
  56. Confer A W, Hall S M, Faulkner C B, Espe B H, Deyoe B L, Morton R J, Smith R A (1985). Effects of challenge dose on the clinical and immune responses of cattle vaccinated with reduced doses of Brucella abortus strain 19. Vet Microbiol, 10(6): 561–575PubMedCrossRefGoogle Scholar
  57. Contreras-Rodriguez A, Ramirez-Zavala B, Contreras A, Schurig G G, Sriranganathan N, Lopez-Merino A (2003). Purification and characterization of an immunogenic aminopeptidase of Brucella melitensis. Infect Immun, 71(9): 5238–5244PubMedCrossRefGoogle Scholar
  58. Cook W E, Williams E S, Thorne E T, Kreeger T J, Stout G, Bardsley K, Edwards H, Schurig G, Colby L A, Enright F (2002). Brucella abortus strain RB51 vaccination in elk. I. Efficacy of reduced dosage. J Wildl Dis, 38: 18–26PubMedGoogle Scholar
  59. Corbel M J (1997). Brucellosis: an overview. Emerg Infect Dis, 3(2): 213–221PubMedCrossRefGoogle Scholar
  60. Crasta O R, Folkerts O, Fei Z, Mane S P, Evans C, Martino-Catt S, Bricker B, Yu G, Du L, Sobral B W (2008). Genome sequence of Brucella abortus vaccine strain S19 compared to virulent strains yields candidate virulence genes. PLoS ONE, 3(5): e2193PubMedCrossRefGoogle Scholar
  61. Da Costa Martins R, Irache J M, Blasco J M, Muñoz M P, Marín C M, Jesús Grilló M, Jesús De Miguel M, Barberán M, Gamazo C (2010). Evaluation of particulate acellular vaccines against Brucella ovis infection in rams. Vaccine, 28(17): 3038–3046PubMedCrossRefGoogle Scholar
  62. Davis D S, Elzer P H (2002). Brucella vaccines in wildlife. Vet Microbiol, 90(1–4): 533–544PubMedCrossRefGoogle Scholar
  63. Davis D S, Templeton J W, Ficht T A, Huber J D, Angus R D, Adams L G (1991). Brucella abortus in Bison. II. Evaluation of strain 19 vaccination of pregnant cows. J Wildl Dis, 27(2): 258–264PubMedGoogle Scholar
  64. Delpino M V, Estein S M, Fossati C A, Baldi P C, Cassataro J (2007). Vaccination with Brucella recombinant DnaK and SurA proteins induces protection against Brucella abortus infection in BALB/c mice. Vaccine, 25(37–38): 6721–6729PubMedCrossRefGoogle Scholar
  65. den Hartigh A B, Sun Y H, Sondervan D, Heuvelmans N, Reinders M O, Ficht T A, Tsolis R M (2004). Differential requirements for VirB1 and VirB2 during Brucella abortus infection. Infect Immun, 72(9): 5143–5149CrossRefGoogle Scholar
  66. Diju I U (2009). Brucellosis—an under-estimated cause of arthralgia & muscular pains in general population. J Ayub Med Coll Abbottabad, 21(2): 128–131PubMedGoogle Scholar
  67. Diptee M D, Adesiyun A A, Asgarali Z, Campbell M, Adone R (2006). Serologic responses, biosafety and clearance of four dosages of Brucella abortus strain RB51 in 6–10 months old water buffalo (Bubalus bubalis). Vet Immunol Immunopathol, 109(1–2): 43–55PubMedCrossRefGoogle Scholar
  68. Dornand J, Lafont V, Oliaro J, Terraza A, Castaneda-Roldan E, Liautard J P (2004). Impairment of intramacrophagic Brucella suis multiplication by human natural killer cells through a contact-dependent mechanism. Infect Immun, 72(4): 2303–2311PubMedCrossRefGoogle Scholar
  69. Dueñas A I, Orduña A, Crespo M S, García-Rodríguez C (2004). Interaction of endotoxins with Toll-like receptor 4 correlates with their endotoxic potential and may explain the proinflammatory effect of Brucella spp. LPS. Int Immunol, 16(10): 1467–1475CrossRefGoogle Scholar
  70. Dzata G K, Confer A W, Wyckoff J H 3rd (1991). The effects of adjuvants on immune responses in cattle injected with a Brucella abortus soluble antigen. Vet Microbiol, 29(1): 27–48PubMedCrossRefGoogle Scholar
  71. Ebel E D, Williams M S, Tomlinson S M (2008). Estimating herd prevalence of bovine brucellosis in 46 USA states using slaughter surveillance. Prev Vet Med, 85(3–4): 295–316PubMedCrossRefGoogle Scholar
  72. Edmonds M D, Cloeckaert A, Elzer P H (2002a). Brucella species lacking the major outer membrane protein Omp25 are attenuated in mice and protect against Brucella melitensis and Brucella ovis. Vet Microbiol, 88(3): 205–221PubMedCrossRefGoogle Scholar
  73. Edmonds M D, Cloeckaert A, Hagius S D, Samartino L E, Fulton W T, Walker J V, Enright F M, Booth N J, Elzer P H (2002b). Pathogenicity and protective activity in pregnant goats of a Brucella melitensis Δaomp25 deletion mutant. Res Vet Sci, 72(3): 235–239PubMedCrossRefGoogle Scholar
  74. Eker A, Uzunca I, Tansel O, Birtane M (2011). A patient with brucellar cervical spondylodiscitis complicated by epidural abscess. J Clin Neurosci, 18(3): 428–430PubMedCrossRefGoogle Scholar
  75. el Idrissi A H, Benkirane A, el Maadoudi M, Bouslikhane M, Berrada J, Zerouali A (2001). Comparison of the efficacy of Brucella abortus strain RB51 and Brucella melitensis Rev. 1 live vaccines against experimental infection with Brucella melitensis in pregnant ewes. Rev Sci Tech, 20(3): 741–747PubMedGoogle Scholar
  76. Elberg S S, Faunce K J Jr (1957). Immunization against Brucella infection. VI. Immunity conferred on goats by a nondependent mutant from a streptomycin-dependent mutant strain of Brucella melitensis. J Bacteriol, 73(2): 211–217PubMedGoogle Scholar
  77. Elzer P H, Edmonds M D, Hagius S D, Walker J V, Gilsdorf M J, Davis D S (1998). Safety of Brucella abortus strain RB51 in Bison. J Wildl Dis, 34(4): 825–829PubMedGoogle Scholar
  78. Entessar F, Ardalan A, Ebadi A, Jones L M (1967). Effect of living Rev. 1 vaccine in producing long-term immunity against Brucella melitensis infection in sheep in Iran. J Comp Pathol, 77(4): 367–376PubMedCrossRefGoogle Scholar
  79. Eschenbrenner M, Horn T A, Wagner M A, Mujer C V, Miller-Scandle T L, DelVecchio V G (2006). Comparative proteome analysis of laboratory grown Brucella abortus 2308 and Brucella melitensis 16M. J Proteome Res, 5(7): 1731–1740PubMedCrossRefGoogle Scholar
  80. Fensterbank R, Pardon P, Marly J (1982). Efficacy of Brucella melitensis Rev. 1 vaccine against Brucella ovis infection in rams. Ann Rech Vet, 13(2): 185–190PubMedGoogle Scholar
  81. Ferguson G P, Datta A, Baumgartner J, Roop R M 2nd, Carlson R W, Walker G C (2004). Similarity to peroxisomal-membrane protein family reveals that Sinorhizobium and Brucella BacA affect lipid-A fatty acids. Proc Natl Acad Sci USA, 101(14): 5012–5017PubMedCrossRefGoogle Scholar
  82. Ferrero M C, Fossati C A, Baldi P C (2009). Smooth Brucella strains invade and replicate in human lung epithelial cells without inducing cell death. Microbes Infect, 11(4): 476–483PubMedCrossRefGoogle Scholar
  83. Fiorentino M A, Campos E, Cravero S, Arese A, Paolicchi F, Campero C, Rossetti O (2008). Protection levels in vaccinated heifers with experimental vaccines Brucella abortus M1-luc and INTA 2. Vet Microbiol, 132(3–4): 302–311PubMedCrossRefGoogle Scholar
  84. Fosgate G T, Adesiyun A A, Hird D W, Johnson W O, Hietala S K, Schurig G G, Ryan J, Diptee M D (2003). Evaluation of brucellosis RB51 vaccine for domestic water buffalo (Bubalus bubalis) in Trinidad. Prev Vet Med, 58(3–4): 211–225PubMedCrossRefGoogle Scholar
  85. Foulongne V, Walravens K, Bourg G, Boschiroli M L, Godfroid J, Ramuz M, O’Callaghan D (2001). Aromatic compound-dependent Brucella suis is attenuated in both cultured cells and mouse models. Infect Immun, 69(1): 547–550PubMedCrossRefGoogle Scholar
  86. Franco M P, Mulder M, Gilman R H, Smits H L (2007). Human brucellosis. Lancet Infect Dis, 7(12): 775–786PubMedCrossRefGoogle Scholar
  87. Galindo R C, Muñoz P M, de Miguel M J, Marin C M, Labairu J, Revilla M, Blasco J M, Gortazar C, de la Fuente J (2010). Gene expression changes in spleens of the wildlife reservoir species, Eurasian wild boar (Sus scrofa), naturally infected with Brucella suis biovar 2. J Genet Genomics, 37(11): 725–736PubMedCrossRefGoogle Scholar
  88. García-Carrillo C (1980). Comparison of B. melitensis Rev. 1 and B. abortus strain 19 as a vaccine against brucellosis in cattle. Zentralbl Veterinarmed B, 27(2): 131–138PubMedCrossRefGoogle Scholar
  89. González D, Grilló M J, De Miguel M J, Ali T, Arce-Gorvel V, Delrue R M, Conde-Alvarez R, Muñoz P, López-Goñi I, Iriarte M, Marín C M, Weintraub A, Widmalm G, Zygmunt M, Letesson J J, Gorvel J P, Blasco J M, Moriyón I (2008). Brucellosis vaccines: assessment of Brucella melitensis lipopolysaccharide rough mutants defective in core and O-polysaccharide synthesis and export. PLoS ONE, 3(7): e2760PubMedCrossRefGoogle Scholar
  90. Graves R R (1943). The story of John M. Buck’s and Matilda’s contribution to the cattle industry. J Am Vet Med Assoc, 102: 193–195Google Scholar
  91. Gulsun S, Aslan S, Satici O, Gul T (2011). Brucellosis in pregnancy. Trop Doct, 41(2): 82–84PubMedCrossRefGoogle Scholar
  92. Haag A F, Myka K K, Arnold M F, Caro-Hernández P, Ferguson G P (2010). Importance of lipopolysaccharide and cyclic β-1,2-glucans in Brucella-mammalian infections. Int J Microbiol, 2010: 1–12Google Scholar
  93. Hall W H (1990). Modern chemotherapy for brucellosis in humans. Rev Infect Dis, 12(6): 1060–1099PubMedCrossRefGoogle Scholar
  94. Halling S M, Peterson-Burch B D, Bricker B J, Zuerner R L, Qing Z, Li L L, Kapur V, Alt D P, Olsen S C (2005). Completion of the genome sequence of Brucella abortus and comparison to the highly similar genomes of Brucella melitensis and Brucella suis. J Bacteriol, 187(8): 2715–2726PubMedCrossRefGoogle Scholar
  95. Herrera E, Rivera A, Palomares E G, Hernández-Castro R, Díaz-Aparicio E (2011). Isolation of Brucella melitensis from a RB51-vaccinated seronegative goat. Trop Anim Health Prod, 43(6): 1069–1070PubMedCrossRefGoogle Scholar
  96. Hofer E, Revilla-Fernández S, Al Dahouk S, Riehm J M, Nöckler K, Zygmunt M S, Cloeckaert A, Tomaso H, Scholz H C (2012). A potential novel Brucella species isolated from mandibular lymph nodes of red foxes in Austria. Vet Microbiol, 155(1): 93–99PubMedCrossRefGoogle Scholar
  97. Jelastopulu E, Bikas C, Petropoulos C, Leotsinidis M (2008). Incidence of human brucellosis in a rural area in Western Greece after the implementation of a vaccination programme against animal brucellosis. BMC Public Health, 8(1): 241–245PubMedCrossRefGoogle Scholar
  98. Jiménez de Bagüés M P, Barberán M, Marín C M, Blasco J M (1995). The Brucella abortus RB51 vaccine does not confer protection against Brucella ovis in rams. Vaccine, 13(3): 301–304PubMedCrossRefGoogle Scholar
  99. Jiménez de Bagués M P, Marín C M, Barberán M, Blasco J M (1989). Responses of ewes to B. melitensis Rev1 vaccine administered by subcutaneous or conjunctival routes at different stages of pregnancy. Ann Rech Vet, 20(2): 205–213PubMedGoogle Scholar
  100. Kaushik P, Singh D K, Kumar S V, Tiwari A K, Shukla G, Dayal S, Chaudhuri P (2010). Protection of mice against Brucella abortus 544 challenge by vaccination with recombinant OMP28 adjuvanted with CpG oligonucleotides. Vet Res Commun, 34(2): 119–132PubMedCrossRefGoogle Scholar
  101. Keller R, Hilton T D, Rios H, Boedeker E C, Kaper J B (2010). Development of a live oral attaching and effacing Escherichia coli vaccine candidate using Vibrio cholerae CVD 103-HgR as antigen vector. Microb Pathog, 48(1): 1–8PubMedCrossRefGoogle Scholar
  102. Kim S, Lee D S, Watanabe K, Furuoka H, Suzuki H, Watarai M (2005). Interferon-γ promotes abortion due to Brucella infection in pregnant mice. BMC Microbiol, 5(1): 1–11CrossRefGoogle Scholar
  103. Kojouri G A, Gholami M (2009). Post vaccination follow-up of Brucella melitensis in blood stream of sheep by PCR assay. Comp Clin Pathol, 18(4): 439–442CrossRefGoogle Scholar
  104. Kolar J (1977). Brucella vaccines production in Mongolia.World Health Organization, Assignment Report on WHO Project MOG BLG 001, SEA/Vaccine/89, 40Google Scholar
  105. Kreeger T J, Cook W E, Edwards W H, Elzer P H, Olsen S C (2002). Brucella abortus strain RB51 vaccination in elk. II. Failure of high dosage to prevent abortion. J Wildl Dis, 38(1): 27–31PubMedGoogle Scholar
  106. Kreeger T J, Miller M W, Wild M A, Elzer P H, Olsen S C (2000). Safety and efficacy of Brucella abortus strain RB51 vaccine in captive pregnant elk. J Wildl Dis, 36(3): 477–483PubMedGoogle Scholar
  107. Kurar E, Splitter G A (1997). Nucleic acid vaccination of Brucella abortus ribosomal L7/L12 gene elicits immune response. Vaccine, 15(17–18): 1851–1857PubMedCrossRefGoogle Scholar
  108. Lavigne J P, Patey G, Sangari F J, Bourg G, Ramuz M, O’Callaghan D, Michaux-Charachon S (2005). Identification of a new virulence factor, BvfA, in Brucella suis. Infect Immun, 73(9): 5524–5529PubMedCrossRefGoogle Scholar
  109. Levine M M, Ferreccio C, Abrego P, Martin O S, Ortiz E, Cryz S (1999). Duration of efficacy of Ty21a, attenuated Salmonella typhi live oral vaccine. Vaccine, 17(Suppl 2): S22–S27PubMedCrossRefGoogle Scholar
  110. Li Y K (1988). A study on one strain of Brucella canis isolated from a cow at the first time. Zhonghua Liu Xing Bing Xue Za Zhi, 9(6): 342–344PubMedGoogle Scholar
  111. Loisel-Meyer S, Jiménez de Bagüés M P, Bassères E, Dornand J, Köhler S, Liautard J P, Jubier-Maurin V (2006). Requirement of norD for Brucella suis virulence in a murine model of in vitro and in vivo infection. Infect Immun, 74(3): 1973–1976PubMedCrossRefGoogle Scholar
  112. Lord V R, Schurig G G, Cherwonogrodzky J W, Marcano M J, Melendez G E (1998). Field study of vaccination of cattle with Brucella abortus strains RB51 and 19 under high and low disease prevalence. Am J Vet Res, 59(8): 1016–1020PubMedGoogle Scholar
  113. Manthei C A (1959). Summary of controlled research with strain 19. Proc Annu Meet US Livest Sanit Assoc, 63: 91–97Google Scholar
  114. Marín C M, Moreno E, Moriyón I, Díaz R, Blasco J M (1999). Performance of competitive and indirect enzyme-linked immunosorbent assays, gel immunoprecipitation with native hapten polysaccharide, and standard serological tests in diagnosis of sheep brucellosis. Clin Diagn Lab Immunol, 6(2): 269–272PubMedGoogle Scholar
  115. Martínez de Tejada G, Pizarro-Cerdá J, Moreno E, Moriyón I (1995). The outer membranes of Brucella spp. are resistant to bactericidal cationic peptides. Infect Immun, 63(8): 3054–3061PubMedGoogle Scholar
  116. Memish Z, Mah M W, Al Mahmoud S, Al Shaalan M, Khan M Y (2000). Brucella bacteraemia: clinical and laboratory observations in 160 patients. J Infect, 40(1): 59–63PubMedCrossRefGoogle Scholar
  117. Minas A, Minas M, Stournara A, Tselepidis S (2004). The “effects” of Rev-1 vaccination of sheep and goats on human brucellosis in Greece. Prev Vet Med, 64(1): 41–47PubMedCrossRefGoogle Scholar
  118. Mingle C K, Manthei C A, Jasmin A M (1941). The stability of reduced virulence exhibited by Brucella abortus strain 19. J Am Vet Med Assoc, 99: 203–204Google Scholar
  119. Moreno E, Moriyón I (2001). Genus Brucella. In Dworkin (ed.), The procaryotes: an evolving microbiological resource for the microbiological community. Springer, New York, NYGoogle Scholar
  120. Moriyón I, Grilló M J, Monreal D, González D, Marín C, López-Goñi I, Mainar-Jaime R C, Moreno E, Blasco J M (2004). Rough vaccines in animal brucellosis: structural and genetic basis and present status. Vet Res, 35(1): 1–38PubMedCrossRefGoogle Scholar
  121. Mukherjee F, Jain J, Grilló M J, Blasco J M, Nair M (2005). Evaluation of Brucella abortus S19 vaccine strains by bacteriological tests, molecular analysis of ery loci and virulence in BALB/c mice. Biologicals, 33(3): 153–160PubMedCrossRefGoogle Scholar
  122. Muñoz P M, de Miguel M J, Grilló M J, Marín C M, Barberán M, Blasco J M (2008). Immunopathological responses and kinetics of Brucella melitensis Rev 1 infection after subcutaneous or conjunctival vaccination in rams. Vaccine, 26(21): 2562–2569PubMedCrossRefGoogle Scholar
  123. Muñoz-Montesino C, Andrews E, Rivers R, González-Smith A, Moraga-Cid G, Folch H, Céspedes S, Oñate A A (2004). Intraspleen delivery of a DNA vaccine coding for superoxide dismutase (SOD) of Brucella abortus induces SOD-specific CD4+ and CD8+ T cells. Infect Immun, 72(4): 2081–2087PubMedCrossRefGoogle Scholar
  124. O’Callaghan D, Maskell D, Liew F Y, Easmon C S, Dougan G (1988). Characterization of aromatic- and purine-dependent Salmonella typhimurium: attention, persistence, and ability to induce protective immunity in BALB/c mice. Infect Immun, 56(2): 419–423PubMedGoogle Scholar
  125. Olsen S C (2010). Brucellosis in the United States: role and significance of wildlife reservoirs. Vaccine, 28(Suppl 5): F73–F76PubMedCrossRefGoogle Scholar
  126. Olsen S C, Boyle S M, Schurig G G, Sriranganathan N N (2009). Immune responses and protection against experimental challenge after vaccination of bison with Brucella abortus strain RB51 or RB51 overexpressing superoxide dismutase and glycosyltransferase genes. Clin Vaccine Immunol, 16(4): 535–540PubMedCrossRefGoogle Scholar
  127. Olsen S C, Fach S J, Palmer M V, Sacco R E, Stoffregen W C, Waters W R (2006). Immune responses of elk to initial and booster vaccinations with Brucella abortus strain RB51 or 19. Clin Vaccine Immunol, 13(10): 1098–1103PubMedCrossRefGoogle Scholar
  128. Olsen S C, Hennager S G (2010). Immune responses and protection against experimental Brucella suis biovar 1 challenge in nonvaccinated or B. abortus strain RB51-vaccinated cattle. Clin Vaccine Immunol, 17(12): 1891–1895PubMedCrossRefGoogle Scholar
  129. Olsen S C, Holland S D (2003). Safety of revaccination of pregnant bison with Brucella abortus strain RB51. J Wildl Dis, 39(4): 824–829PubMedGoogle Scholar
  130. Olsen S C, Jensen A E, Stoffregen W C, Palmer M V (2003). Efficacy of calfhood vaccination with Brucella abortus strain RB51 in protecting bison against brucellosis. Res Vet Sci, 74(1): 17–22PubMedCrossRefGoogle Scholar
  131. Oñate A A, Donoso G, Moraga-Cid G, Folch H, Céspedes S, Andrews E (2005). An RNA vaccine based on recombinant Semliki Forest virus particles expressing the Cu, Zn superoxide dismutase protein of Brucella abortus induces protective immunity in BALB/c mice. Infect Immun, 73(6): 3294–3300PubMedCrossRefGoogle Scholar
  132. Osorio M, Wu Y, Singh S, Merkel T J, Bhattacharyya S, Blake M S, Kopecko D J (2009). Anthrax protective antigen delivered by Salmonella enterica serovar Typhi Ty21a protects mice from a lethal anthrax spore challenge. Infect Immun, 77(4): 1475–1482PubMedCrossRefGoogle Scholar
  133. Palmer M V, Cheville N F, Jensen A E (1996a). Experimental infection of pregnant cattle with the vaccine candidate Brucella abortus strain RB51: pathologic, bacteriologic, and serologic findings. Vet Pathol, 33(6): 682–691PubMedCrossRefGoogle Scholar
  134. Palmer M V, Olsen S C, Gilsdorf M J, Philo L M, Clarke P R, Cheville N F (1996b). Abortion and placentitis in pregnant bison (Bison bison) induced by the vaccine candidate, Brucella abortus strain RB51. Am J Vet Res, 57(11): 1604–1607PubMedGoogle Scholar
  135. Pappas G, Akritidis N, Bosilkovski M, Tsianos E (2005). Brucellosis. N Engl J Med, 352(22): 2325–2336PubMedCrossRefGoogle Scholar
  136. Pappas G, Panagopoulou P, Christou L, Akritidis N (2006a). Brucella as a biological weapon. Cell Mol Life Sci, 63(19–20): 2229–2236PubMedCrossRefGoogle Scholar
  137. Pappas G, Papadimitriou P, Akritidis N, Christou L, Tsianos E V (2006b). The new global map of human brucellosis. Lancet Infect Dis, 6(2): 91–99PubMedCrossRefGoogle Scholar
  138. Pasquevich K A, Estein S M, García Samartino C, Zwerdling A, Coria L M, Barrionuevo P, Fossati C A, Giambartolomei G H, Cassataro J (2009). Immunization with recombinant Brucella species outer membrane protein Omp16 or Omp19 in adjuvant induces specific CD4+ and CD8+ T cells as well as systemic and oral protection against Brucella abortus infection. Infect Immun, 77(1): 436–445PubMedCrossRefGoogle Scholar
  139. Petrovska L, Hewinson R G, Dougan G, Maskell D J, Woodward M J (1999). Brucella melitensis 16M: characterisation of the galE gene and mouse immunisation studies with a galE deficient mutant. Vet Microbiol, 65(1): 21–36PubMedCrossRefGoogle Scholar
  140. Phillips R W, Elzer P H, Robertson G T, Hagius S D, Walker J V, Fatemi M B, Enright F M, Roop R M 2nd (1997). A Brucella melitensis high-temperature-requirement A (htrA) deletion mutant is attenuated in goats and protects against abortion. Res Vet Sci, 63(2): 165–167PubMedCrossRefGoogle Scholar
  141. Pishva E, Salehi M (2008). First report of isolation of Brucella melitensis, vaccine strain Rev.1 as a source of cattle infection in Iran. J Sci Islam Repub Iran, 19: 19–23Google Scholar
  142. Poester F P, Goncalves V S, Paixao T A, Santo, R L, Olsen S C, Schurig G G, Lage A P (2006). Efficacy of strain RB51 vaccine in heifers against experimental brucellosis. Vaccine, 24: 5327–5334PubMedCrossRefGoogle Scholar
  143. Pontes D S, Dorella F A, Ribeiro L A, Miyoshi A, Le Loir Y, Gruss A, Oliveira S C, Langella P, Azevedo V (2003). Induction of partial protection in mice after oral administration of Lactococcus lactis producing Brucella abortus L7/L12 antigen. J Drug Target, 11(8–10): 489–493PubMedCrossRefGoogle Scholar
  144. Pourbagher M A, Pourbagher A, Savas L, Turunc T, Demiroglu Y Z, Erol I, Yalcintas D (2006). Clinical pattern and abdominal sonographic findings in 251 cases of brucellosis in southern Turkey. AJR Am J Roentgenol, 187(2): W191–4PubMedCrossRefGoogle Scholar
  145. Pugh G W J Jr, Tabatabai L B, Bricker B J, Mayfield J E, Phillips M, Zehr E S, Belzer C A (1990). Immunogenicity of Brucella-extracted and recombinant protein vaccines in CD-1 and BALB/c mice. Am J Vet Res, 51(9): 1413–1420PubMedGoogle Scholar
  146. Radwan A I, Bekairi S I, Mukayel A A, al-Bokmy A M, Prasad P V, Azar F N, Coloyan E R (1995). Control of Brucella melitensis infection in a large camel herd in Saudi Arabia using antibiotherapy and vaccination with Rev. 1 vaccine. Rev Sci Tech, 14(3): 719–732PubMedGoogle Scholar
  147. Rafiei A, Ardestani S K, Kariminia A, Keyhani A, Mohraz M, Amirkhani A (2006). Dominant Th1 cytokine production in early onset of human brucellosis followed by switching towards Th2 along prolongation of disease. J Infect, 53(5): 315–324PubMedCrossRefGoogle Scholar
  148. Rajasekaran P, Surendran N, Seleem M N, Sriranganathan N, Schurig G G, Boyle S M (2011). Over-expression of homologous antigens in a leucine auxotroph of Brucella abortus strain RB51 protects mice against a virulent B. suis challenge. Vaccine, 29(17): 3106–3110PubMedCrossRefGoogle Scholar
  149. Rajashekara G, Krepps M, Eskra L, Mathison A, Montgomery A, Ishii Y, Splitter G (2005). Unraveling Brucella genomics and pathogenesis in immunocompromised IRF-1−/− mice. Am J Reprod Immunol, 54(6): 358–368PubMedCrossRefGoogle Scholar
  150. Robertson G T, Elzer P H, Roop R M 2nd (1996). In vitro and in vivo phenotypes resulting from deletion of the high temperature requirement A (htrA) gene from the bovine vaccine strain Brucella abortus S19. Vet Microbiol, 49(3–4): 197–207PubMedCrossRefGoogle Scholar
  151. Roop R M 2nd, Jeffers G, Bagchi T, Walker J, Enright F M, Schurig G G (1991). Experimental infection of goat fetuses in utero with a stable, rough mutant of Brucella abortus. Res Vet Sci, 51(2): 123–127PubMedCrossRefGoogle Scholar
  152. Roop R M 2nd, Phillips R W, Hagius S, Walker J V, Booth N J, Fulton W T, Edmonds M D, Elzer P H (2001). Re-examination of the role of the Brucella melitensis HtrA stress response protease in virulence in pregnant goats. Vet Microbiol, 82(1): 91–95PubMedCrossRefGoogle Scholar
  153. Roth F, Zinsstag J, Orkhon D, Chimed-Ochir G, Hutton G, Cosivi O, Carrin G, Otte J (2003). Human health benefits from livestock vaccination for brucellosis: case study. Bull World Health Organ, 81(12): 867–876PubMedGoogle Scholar
  154. Sangari F J, Agüero J (1994). Identification of Brucella abortus B19 vaccine strain by the detection of DNA polymorphism at the ery locus. Vaccine, 12(5): 435–438PubMedCrossRefGoogle Scholar
  155. Sangari F J, García-Lobo J M, Agüero J (1994). The Brucella abortus vaccine strain B19 carries a deletion in the erythritol catabolic genes. FEMS Microbiol Lett, 121(3): 337–342PubMedCrossRefGoogle Scholar
  156. Schlabritz-Loutsevitch N E, Whatmore A M, Quance C R, Koylass M S, Cummins L B, Dick E J Jr, Snider C L, Cappelli D, Ebersole J L, Nathanielsz P W, Hubbard G B (2009). A novel Brucella isolate in association with two cases of stillbirth in non-human primates — first report. J Med Primatol, 38(1): 70–73PubMedCrossRefGoogle Scholar
  157. Schurig G G, Roop R M 2nd, Bagchi T, Boyle S, Buhrman D, Sriranganathan N (1991). Biological properties of RB51; a stable rough strain of Brucella abortus. Vet Microbiol, 28(2): 171–188PubMedCrossRefGoogle Scholar
  158. SCOFCAH (2011). Portugal: Results of the implementation of the sheep and goat brucellosis eradication programme 2010 Standing Committee on the Food Chain and Animal Health (SCOFCAH), Brussels
  159. Scurlock B M, Edwards W H (2010). Status of brucellosis in free-ranging elk and bison in Wyoming. J Wildl Dis, 46(2): 442–449PubMedGoogle Scholar
  160. Shi D, Song Y, Li Y J (2006). Progress on lactococcus lactis expressing heterologous antigens as live mucosal vaccines. Wei Sheng Wu Xue Bao, 46(4): 680–683PubMedGoogle Scholar
  161. Silva T M, Costa E A, Paixão T A, Tsolis R M, Santos R L (2011a). Laboratory animal models for brucellosis research. J Biomed Biotechnol, 2011: 518323PubMedCrossRefGoogle Scholar
  162. Silva T M, Paixão T A, Costa E A, Xavier M N, Sá J C, Moustacas V S, den Hartigh A B, Carvalho Neta A V, Oliveira S C, Tsolis R, Santos R L (2011b). Putative ATP-binding cassette transporter is essential for Brucella ovis pathogenesis in mice. Infect Immun, 79(4): 1706–1717PubMedCrossRefGoogle Scholar
  163. Smith L D, Ficht T A (1990). Pathogenesis of Brucella. Crit Rev Microbiol, 17(3): 209–230PubMedCrossRefGoogle Scholar
  164. Smither S J, Perkins S D, Davies C, Stagg A J, Nelson M, Atkins H S (2009). Development and characterization of mouse models of infection with aerosolized Brucella melitensis and Brucella suis. Clin Vaccine Immunol, 16(5): 779–783PubMedCrossRefGoogle Scholar
  165. Spink W W, Hall J W 3rd, Finstad J, Mallet E (1962). Immunization with viable Brucella organisms. Results of a safety test in humans. Bull World Health Organ, 26: 409–419PubMedGoogle Scholar
  166. Stabel T J, Mayfield J E, Morfitt D C, Wannemuehler M J (1993). Oral immunization of mice and swine with an attenuated Salmonella choleraesuis [delta cya-12 delta(crp-cdt)19] mutant containing a recombinant plasmid. Infect Immun, 61(2): 610–618PubMedGoogle Scholar
  167. Stabel T J, Mayfield J E, Tabatabai L B, Wannemuehler M J (1990). Oral immunization of mice with attenuated Salmonella typhimurium containing a recombinant plasmid which codes for production of a 31-kilodalton protein of Brucella abortus. Infect Immun, 58(7): 2048–2055PubMedGoogle Scholar
  168. Stabel T J, Mayfield J E, Tabatabai L B, Wannemuehler M J (1991). Swine immunity to an attenuated Salmonella typhimurium mutant containing a recombinant plasmid which codes for production of a 31-kilodalton protein of Brucella abortus. Infect Immun, 59(9): 2941–2947PubMedGoogle Scholar
  169. Stevens M G, Hennager S G, Olsen S C, Cheville N F (1994). Serologic responses in diagnostic tests for brucellosis in cattle vaccinated with Brucella abortus 19 or RB51. J Clin Microbiol, 32(4): 1065–1066PubMedGoogle Scholar
  170. Stevens M G, Olsen S C (1996). Antibody responses to Brucella abortus 2308 in cattle vaccinated with B. abortus RB51. Infect Immun, 64(3): 1030–1034PubMedGoogle Scholar
  171. Stevens M G, Olsen S C, Cheville N F (1995a). Comparative analysis of immune responses in cattle vaccinated with Brucella abortus strain 19 or strain RB51. Vet Immunol Immunopathol, 44(3–4): 223–235PubMedCrossRefGoogle Scholar
  172. Stevens M G, Olsen S C, Pugh G W Jr, Brees D (1995b). Comparison of immune responses and resistance to brucellosis in mice vaccinated with Brucella abortus 19 or RB51. Infect Immun, 63(1): 264–270PubMedGoogle Scholar
  173. Taylor A W, McDiarmid A (1949). The stability of the avirulent characters of Brucella abortus, strain 19 and strain 45/20 in lactating and pregnant cows. Vet Rec, 61: 317–318Google Scholar
  174. Teske S S, Huang Y, Tamrakar S B, Bartrand T A, Weir M H, Haas C N (2011). Animal and human dose-response models for Brucella species. Risk Anal, 31(10): 1576–1596PubMedCrossRefGoogle Scholar
  175. Thorne E T (1997). Brucellosis, bison, elk, and cattle in the Greater Yellowstone area: defining the problem, exploring solutions. Cheyenne, Wyoming Game and Fish Dept. for Greater Yellowstone Interagency Brucellosis CommitteeGoogle Scholar
  176. Tibor A, Jacques I, Guilloteau L, Verger J M, Grayon M, Wansard V, Letesson J J (1998). Effect of P39 gene deletion in live Brucella vaccine strains on residual virulence and protective activity in mice. Infect Immun, 66(11): 5561–5564PubMedGoogle Scholar
  177. Trant C G, Lacerda T L, Carvalho N B, Azevedo V, Rosinha G M, Salcedo S P, Gorvel J P, Oliveira S C (2010). The Brucella abortus phosphoglycerate kinase mutant is highly attenuated and induces protection superior to that of vaccine strain 19 in immunocompromised and immunocompetent mice. Infect Immun, 78(5): 2283–2291PubMedCrossRefGoogle Scholar
  178. Treanor J J, Johnson J S, Wallen R L, Cilles S, Crowley P H, Cox J J, Maehr D S, White P J, Plumb G E (2010). Vaccination strategies for managing brucellosis in Yellowstone bison. Vaccine, 28(Suppl 5): F64–F72PubMedCrossRefGoogle Scholar
  179. Ugalde J E, Comerci D J, Leguizamón M S, Ugalde R A (2003). Evaluation of Brucella abortus phosphoglucomutase (pgm) mutant as a new live rough-phenotype vaccine. Infect Immun, 71(11): 6264–6269PubMedCrossRefGoogle Scholar
  180. Valderas M W, Barrow W W (2008). Establishment of a method for evaluating intracellular antibiotic efficacy in Brucella abortus-infected Mono Mac 6 monocytes. J Antimicrob Chemother, 61(1): 128–134PubMedCrossRefGoogle Scholar
  181. Van Campen H, Rhyan J (2010). The role of wildlife in diseases of cattle. Vet Clin North Am Food Anim Pract, 26(1): 147–161PubMedCrossRefGoogle Scholar
  182. Velikovsky C A, Cassataro J, Giambartolomei G H, Goldbaum F A, Estein S, Bowden R A, Bruno L, Fossati C A, Spitz M (2002). A DNA vaccine encoding lumazine synthase from Brucella abortus induces protective immunity in BALB/c mice. Infect Immun, 70(5): 2507–2511PubMedCrossRefGoogle Scholar
  183. Vemulapalli R, Contreras A, Sanakkayala N, Sriranganathan N, Boyle S M, Schurig G G (2004). Enhanced efficacy of recombinant Brucella abortus RB51 vaccines against B. melitensis infection in mice. Vet Microbiol, 102(3–4): 237–245PubMedCrossRefGoogle Scholar
  184. Verger J M, Grayon M, Zundel E, Lechopier P, Olivier-Bernardin V (1995). Comparison of the efficacy of Brucella suis strain 2 and Brucella melitensis Rev. 1 live vaccines against a Brucella melitensis experimental infection in pregnant ewes. Vaccine, 13(2): 191–196PubMedCrossRefGoogle Scholar
  185. Walker G C, LeVier K, Phillips R W, Grippe V K, Roop R M, 2nd (2000). Similar requirements of a plant symbiont and a mammalian pathogen for prolonged intracellular survival. Science, 287: 2492–2493PubMedCrossRefGoogle Scholar
  186. Wang Y, Bai Y, Qu Q, Xu J, Chen Y, Zhong Z, Qiu Y, Wang T, Du X, Wang Z, Yu S, Fu S, Yuan J, Zhen Q, Yu Y, Chen Z, Huang L (2011). The 16MΔvjbR as an ideal live attenuated vaccine candidate for differentiation between Brucella vaccination and infection. Vet Microbiol, 151(3–4): 354–362PubMedCrossRefGoogle Scholar
  187. Ward D, Jackson, R., Karomatullo H, Khakimov T, Kurbonov K, Amirbekov M, Stack J, El-Idrissi A, Heuer C (2011). Brucellosis control in Tajikistan using Rev 1 vaccine: change in seroprevalence in small ruminants from 2004 to 2009. Vet RecGoogle Scholar
  188. Whatmore A M (2009). Current understanding of the genetic diversity of Brucella, an expanding genus of zoonotic pathogens. Infect Genet Evol, 9(6): 1168–1184PubMedCrossRefGoogle Scholar
  189. Winter A J, Rowe G E, Duncan J R, Eis M J, Widom J, Ganem B, Morein B (1988). Effectiveness of natural and synthetic complexes of porin and O polysaccharide as vaccines against Brucella abortus in mice. Infect Immun, 56(11): 2808–2817PubMedGoogle Scholar
  190. Wise R I (1980). Brucellosis in the United States. Past, present, and future. JAMA, 244(20): 2318–2322Google Scholar
  191. Wyckoff J H 3rd, Howland J L, Scott C M, Smith R A, Confer A W (2005). Recombinant bovine interleukin 2 enhances immunity and protection induced by Brucella abortus vaccines in cattle. Vet Microbiol, 111(1–2): 77–87PubMedCrossRefGoogle Scholar
  192. Xavier M N, Paixão T A, Poester F P, Lage A P, Santos R L (2009). Pathological, immunohistochemical and bacteriological study of tissues and milk of cows and fetuses experimentally infected with Brucella abortus. J Comp Pathol, 140(2–3): 149–157PubMedCrossRefGoogle Scholar
  193. Xin X (1986). Orally administrable brucellosis vaccine: Brucella suis strain 2 vaccine. Vaccine, 4(4): 212–216PubMedCrossRefGoogle Scholar
  194. Yang X, Becker T, Walters N, Pascual D W (2006). Deletion of znuA virulence factor attenuates Brucella abortus and confers protection against wild-type challenge. Infect Immun, 74(7): 3874–3879PubMedCrossRefGoogle Scholar
  195. Yang X, Hinnebusch B J, Trunkle T, Bosio C M, Suo Z, Tighe M, Harmsen A, Becker T, Crist K, Walters N, Avci R, Pascual D W (2007). Oral vaccination with salmonella simultaneously expressing Yersinia pestis F1 and V antigens protects against bubonic and pneumonic plague. J Immunol, 178(2): 1059–1067PubMedGoogle Scholar
  196. Yang X, Hudson M, Walters N, Bargatze R F, Pascual D W (2005). Selection of protective epitopes for Brucella melitensis by DNA vaccination. Infect Immun, 73(11): 7297–7303PubMedCrossRefGoogle Scholar
  197. Yang X, Thornburg T, Walters N, Pascual D W (2010). ΔznuAΔapurE Brucella abortus 2308 mutant as a live vaccine candidate. Vaccine, 28(4): 1069–1074PubMedCrossRefGoogle Scholar
  198. Yang Y, Yin J, Guo D, Lang X, Wang X (2011). Immunization of mice with recombinant S-adenosyl-L-homocysteine hydrolase protein confers protection against Brucella melitensis infection. FEMS Immunol Med Microbiol, 61(2): 159–167PubMedCrossRefGoogle Scholar
  199. Young E J (1989). Clinical manifestations of human brucellosis, p. 97–126. In E. J. Young and M. J. Corbel (ed.), Brucellosis: clinical and laboratory aspects. CRC Press, Inc, Boca Raton, FlaGoogle Scholar
  200. Yu D H, Hu X D, Cai H, Li M (2007). A combined DNA vaccine encoding BCSP31, SOD, and L7/L12 confers high protection against Brucella abortus 2308 by inducing specific CTL responses. DNA Cell Biol, 26(6): 435–443PubMedCrossRefGoogle Scholar
  201. Zhan Y, Cheers C (1993). Endogenous gamma interferon mediates resistance to Brucella abortus infection. Infect Immun, 61(11): 4899–4901PubMedGoogle Scholar
  202. Zhao Z, Li M, Luo D, Xing L, Wu S, Duan Y, Yang P, Wang X (2009). Protection of mice from Brucella infection by immunization with attenuated Salmonella enterica serovar typhimurium expressing A L7/L12 and BLS fusion antigen of Brucella. Vaccine, 27(38): 5214–5219PubMedCrossRefGoogle Scholar
  203. Zinsstag J, Roth F, Orkhon D, Chimed-Ochir G, Nansalmaa M, Kolar J, Vounatsou P (2005). A model of animal-human brucellosis transmission in Mongolia. Prev Vet Med, 69(1–2): 77–95PubMedCrossRefGoogle Scholar
  204. Zowghi E, Ebadi A (1985). Naturally occurring Brucella melitensis infection in cattle in Iran. Rev Sci Tech Off Int Epiz, 4: 811–814Google Scholar

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© Higher Education Press and Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Xinghong Yang
    • 1
    Email author
  • Jerod A. Skyberg
    • 1
  • Ling Cao
    • 1
  • Beata Clapp
    • 1
  • Theresa Thornburg
    • 1
  • David W. Pascual
    • 1
  1. 1.Department of Immunology Infectious DiseasesMontana State UniversityBozemanUSA

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