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Review

Confronting the barriers to develop novel vaccines against brucellosis

, &
Pages 1291-1305 | Published online: 09 Jan 2014

References

  • Carvalho Neta AV, Mol JP, Xavier MN et al. Pathogenesis of bovine brucellosis. Vet. J.184(2), 146–155 (2010).
  • Pappas G, Akritidis N, Bosilkovski M et al. Brucellosis. N. Engl. J. Med.352(22), 2325–2336 (2005).
  • Nicoletti P. Vaccination against Brucella. Adv. Biotechnol. Processes13, 147–168 (1990).
  • Nicoletti P. Vaccination. In: Animal Brucellosis. Nielsen K, Dunca JR (Eds). CRC Press, Boca Raton, FL, USA, 284–299 (1990).
  • Schurig GG, Roop RM 2nd, Bagchi T et al. Biological properties of RB51; a stable rough strain of Brucella abortus. Vet. Microbiol.28(2), 171–188 (1991).
  • Marianelli C, Ciuchini F, Tarantino M et al. Genetic bases of the rifampin resistance phenotype in Brucella spp. J. Clin. Microbiol.42(12), 5439–5443 (2004).
  • Moriyon I, Grillo MJ, Monreal D et al. Rough vaccines in animal brucellosis: structural and genetic basis and present status. Vet. Res.35(1), 1–38 (2004).
  • Adams LG. Development of live Brucella vaccines. In: Advances in Brucellosis Research. Adams LG (Ed.). Texas: A & M University Press, TX, USA, 205–276 (1990).
  • Dornand J, Gross A, Lafont V et al. The innate immune response against Brucella in humans. Vet. Microbiol.90(1–4), 383–394 (2002).
  • Golding B, Scott DE, Scharf O et al. Immunity and protection against Brucella abortus. Microbes. Infect.3(1), 43–48 (2001).
  • Kawai T, Akira S. TLR signaling. Semin. Immunol.19, 24–32 (2007).
  • Medzhitov R. Recognition of microorganisms and activation of the immune response. Nature449(7164), 819–826 (2007).
  • Campos MA, Rosinha GM, Almeida IC et al. Role of Toll-like receptor 4 in induction of cell-mediated immunity and resistance to Brucella abortus infection in mice. Infect. Immun.72(1), 176–186 (2004).
  • Weiss DS, Takeda K, Akira S et al. MyD88, but not Toll-like receptors 4 and 2, is required for efficient clearance of Brucella abortus. Infect. Immun.73(8), 5137–5143 (2005).
  • Macedo GC, Magnani DM, Carvalho NB et al. Central role of MyD88-dependent dendritic cell maturation and proinflammatory cytokine production to control Brucella abortus infection. J. Immunol.180(2), 1080–1087 (2008).
  • Copin R, De Baetselier P, Carlier Y et al. MyD88-dependent activation of B220-CD11b+LY-6C+ dendritic cells during Brucella melitensis infection. J. Immunol.178(8), 5182–5191 (2007).
  • Araya LN, Elzer PH, Rowe GE et al. Temporal development of protective cell-mediated and humoral immunity in BLAB/c mice infected with Brucella abortus. J. Immunol.143, 3330–3337 (1989).
  • Oliveira SC, Splitter GA. CD8+ type 1 CD44hi CD45 RBlo T lymphocytes control intracellular Brucella abortus infection as demonstrated in major histocompatibility complex class I- and class II-deficient mice. Eur. J. Immunol.25(9), 2551–2557 (1995).
  • Oliveira SC, Harms JS, Rech EL et al. The role of T cell subsets and cytokines in the regulation of intracellular bacterial infection. Braz. J. Med. Biol. Res.31, 77–84 (1998).
  • Murphy EA, Sathiyaseelan J, Parent MA et al. Interferon-γ is crucial for surviving a Brucella abortus infection in both resistant C57BL/6 and susceptible BALB/c mice. Immunology103(4), 511–518 (2001).
  • Jiang X, Baldwin CL. Effects of cytokines on intracellular growth of Brucella abortus. Infect. Immun.61(1), 124–134 (1993).
  • Barquero-Calvo E, Chaves-Olarte E, Weiss DS et al.Brucella abortus uses a stealthy strategy to avoid activation of the innate immune system during the onset of infection. PLoS One2(7), e631 (2007).
  • Fretin D, Fauconnier A, Kohler S et al. The sheathed flagellum of Brucella melitensis is involved in persistence in a murine model of infection. Cell. Microbiol.7(5), 687–698 (2005).
  • Andersen-Nissen E, Smith KD, Strobe KL et al. Evasion of Toll-like receptor 5 by flagellated bacteria. Proc. Natl Acad. Sci. USA102(26), 9247–9252 (2005).
  • Lapaque N, Muller A, Alexopoulou L et al.Brucella abortus induces Irgm3 and Irga6 expression via type-I IFN by a MyD88-dependent pathway, without the requirement of TLR-2, TLR-4, TLR-5 and TLR-9. Microb. Pathog.47(6), 299–304 (2009).
  • Cardoso PG, Macedo GC, Azevedo V et al.Brucella spp noncanonical LPS: structure, biosynthesis, and interaction with host immune system. Microb. Cell. Fact.5, 13 (2006).
  • Lapaque N, Moriyon I, Moreno E et al.Brucella lipopolysaccharide acts as a virulence factor. Curr. Opin. Microbiol.8(1), 60–66 (2005).
  • Barquero-Calvo E, Conde-Alvarez R, Chacon-Diaz C et al. The differential interaction of Brucella and ochrobactrum with innate immunity reveals traits related to the evolution of stealthy pathogens. PLoS One4(6), e5893 (2009).
  • Pei J, Turse JE, Ficht TA et al. Evidence of Brucella abortus OPS dictating uptake and restricting NF-κB activation in murine macrophages. Microbes. Infect.10(6), 582–590 (2008).
  • Forestier C, Deleuil F, Lapaque N et al.Brucella abortus lipopolysaccharide in murine peritoneal macrophages acts as a down-regulator of T cell activation. J. Immunol.165(9), 5202–5210 (2000).
  • Barrionuevo P, Cassataro J, Delpino MV et al.Brucella abortus inhibits major histocompatibility complex class II expression and antigen processing through interleukin-6 secretion via Toll-like receptor 2. Infect. Immun.76(1), 250–262 (2008).
  • Porte F, Naroeni A, Ouahrani-Bettache S et al. Role of the Brucella suis lipopolysaccharide O antigen in phagosomal genesis and in inhibition of phagosome-lysosome fusion in murine macrophages. Infect. Immun.71(3), 1481–1490 (2003).
  • Pizarro-Cerda J, Meresse S, Parton RG et al.Brucella abortus transits through the autophagic pathway and replicates in the endoplasmic reticulum of nonprofessional phagocytes. Infect. Immun.66(12), 5711–5724 (1998).
  • Celli J, de Chastellier C, Franchini DM et al.Brucella evades macrophage killing via VirB-dependent sustained interactions with the endoplasmic reticulum. J. Exp. Med.198(4), 545–556 (2003).
  • Gorvel JP. Brucella: a Mr ‘Hide’ converted into Dr Jekyll. Microbes. Infect.10(9), 1010–1013 (2008).
  • Arellano-Reynoso B, Lapaque N, Salcedo S et al. Cyclic β-1,2-glucan is a Brucella virulence factor required for intracellular survival. Nat. Immunol.6(6), 618–625 (2005).
  • Cirl C, Wieser A, Yadav M et al. Subversion of Toll-like receptor signaling by a unique family of bacterial Toll/interleukin-1 receptor domain-containing proteins. Nat. Med.14(4), 399–406 (2008).
  • Radhakrishnan GK, Yu Q, Harms JS et al.Brucella TIR domain-containing protein mimics properties of the Toll-like receptor adaptor protein TIRAP. J. Biol. Chem.284(15), 9892–9898 (2009).
  • Salcedo SP, Marchesini MI, Lelouard H et al.Brucella control of dendritic cell maturation is dependent on the TIR-containing protein Btp1. PLoS Pathog.4(2), e21 (2008).
  • Sengupta D, Koblansky A, Gaines J et al. Subversion of innate immune responses by Brucella through the targeted degradation of the TLR signaling adapter, MAL. J. Immunol.184(2), 956–964 (2010).
  • Schijns VE. Immunological concepts of vaccine adjuvant activity. Curr. Opin. Immunol.12, 456–463 (2000).
  • Lima KM, dos Santos SA, Rodrigues JM Jr et al. Vaccine adjuvant: it makes the difference. Vaccine22(19), 2374–2379 (2004).
  • Reed SG, Bertholet S, Coler RN et al. New horizons in adjuvants for vaccine development. Trends Immunol.30, 23–32 (2009).
  • Oliveira SC, Splitter GA. Immunization of mice with recombinant L7/L12 ribosomal protein confers protection against Brucella abortus infection. Vaccine14(10), 959–962 (1996).
  • Mallick AI, Singha H, Chaudhuri P et al. Liposomised recombinant ribosomal L7/L12 protein protects BALB/c mice against Brucella abortus 544 infection. Vaccine25, 3692–3704 (2007).
  • Mallick AI, Singha H, Khan S et al. Escheriosome-mediated delivery of recombinant ribosomal L7/L12 protein confers protection against murine brucellosis. Vaccine25, 7873–7884 (2007).
  • Yang Y, Yin J, Guo D et al. Immunization of mice with recombinant S-adenosyl-L-homocysteine hydrolase protein confers protection against Brucella melitensis infection. FEMS Immunol. Med. Microbiol.61(2), 159–167 (2011).
  • Velikovsky CA, Goldbaum FA, Cassataro J et al.Brucella lumazine synthase elicits a mixed Th1-Th2 immune response and reduces infection in mice challenged with Brucella abortus 544 independently of the adjuvant formulation used. Infect. Immun.71, 5750–5755 (2003).
  • Zylberman V, Craig PO, Klinke S et al. High order quaternary arrangement confers increased structural stability to Brucella sp. lumazine synthase. J. Biol. Chem.279, 8093–8101 (2004).
  • Berguer PM, Mundinano J, Piazzon I et al. A polymeric bacterial protein activates dendritic cells via TLR-4. J. Immunol.176, 2366–2372 (2006).
  • Velikovsky CA, Cassataro J, Giambartolomei GH et al. A DNA vaccine encoding lumazine synthase from Brucella abortus induces protective immunity in BALB/c mice. Infect. Immun.70, 2507–2511 (2002).
  • Cassataro J, Estein SM, Pasquevich KA et al. 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, 8079–8088 (2005).
  • Aucouturier J, Dupuis L, Ganne V. Adjuvants designed for veterinary and human vaccines. Vaccine19, 2666–2672 (2001).
  • Kwissa M, Kasturi SP, Pulendran B. The science of adjuvants. Expert Rev. Vaccines6(5), 673–684 (2007).
  • Denisov AA, Korobovtseva YS, Karpova OM et al. Immunopotentiation of live brucellosis vaccine by adjuvants. Vaccine1(28), 17–22 (2010).
  • Al-Mariri A, Tibor A, Mertens P et al. 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, 4816–4822 (2001).
  • Kaushik P, Singh DK, Kumar SV et al. Protection of mice against Brucella abortus 544 challenge by vaccination with recombinant OMP28 adjuvanted with CpG oligonucleotides. Vet. Res. Commun.34, 119–132 (2010).
  • Cassataro J, Velikovsky CA, Giambartolomei GH et al. Immunogenicity of the Brucella melitensis recombinant ribosome recycling factor-homologous protein and its cDNA. Vaccine20, 1660–1669 (2002).
  • Leclerq S, Harms JS, Rosinha GM et al. Induction of a Th1-type of immune response but not protective immunity by intramuscular DNA immunisation with Brucella abortus GroEL heat-shock gene. J. Med. Microbiol.51, 20–26 (2002).
  • Bae JE, Schurig GG, Toth TE. Mice immune responses to Brucella abortus heat shock proteins. Use of baculovirus recombinant-expressing whole insect cells, purified Brucella abortus recombinant proteins, and a vaccinia virus recombinant as immunogens. Vet. Microbiol.88, 189–202 (2002).
  • Demotz S, Moulon C, Roggero MA et al. Native-like, long synthetic peptides as components of sub-unit vaccines: practical and theoretical considerations for their use in humans. Mol. Immunol.38, 415–422 (2001).
  • Tabatabai LB, Pugh GW Jr. Modulation of immune responses in Balb/c mice vaccinated with Brucella abortus Cu-Zn superoxide dismutase synthetic peptide vaccine. Vaccine12, 919–924 (1994).
  • Vizcaino N, Kittelberger R, Cloeckaert A et al. Minor nucleotide substitutions in the omp31 gene of Brucella ovis result in antigenic differences in the major outer membrane protein that it encodes compared with those of the other Brucella species. Infect. Immun.69, 7020–7028 (2001).
  • Delpino MV, Estein SM, Fossati CA et al. Vaccination with Brucella recombinant DnaK and SurA proteins induces protection against Brucella abortus infection in BALB/c mice. Vaccine25, 6721–6729 (2007).
  • Cassataro J, Pasquevich KA, Estein SM et al. A recombinant subunit vaccine based on the insertion of 27 amino acids from Omp31 to the N-terminus of BLS induced a similar degree of protection against B. ovis than Rev.1 vaccination. Vaccine25, 4437–4446 (2007).
  • Dagan R, Eskola J, Leclerc C et al. Reduced response to multiple vaccines sharing common protein epitopes that are administered simultaneously to infants. Infect. Immun.66, 2093–2098 (1998).
  • Singh RA, Rodgers JR, Barry MA. The role of T cell antagonism and original antigenic sin in genetic immunization. J. Immunol.169, 6779–6786 (2002).
  • Laplagne DA, Zylberman V, Ainciart N et al. Engineering of a polymeric bacterial protein as a scaffold for the multiple display of peptides. Proteins57, 820–828 (2004).
  • Delpino MV, Marchesini MI, Estein SM et al. A bile salt hydrolase of Brucella abortus contributes to the establishment of a successful infection through the oral route in mice. Infect. Immun.75, 299–305 (2007).
  • Pasquevich KA, Estein SM, Samartino CG et al. 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, 436–445 (2009).
  • Yang X, Walters N, Robison A et al. Nasal immunization with recombinant Brucella melitensis bp26 and trigger factor with cholera toxin reduces B. melitensis colonization. Vaccine25, 2261–2268 (2007).
  • Holmgren J, Czerkinsky C. Mucosal immunity and vaccines. Nat. Med.11, 45–53 (2005).
  • Pasquevich KA, Garcia Samartino C, Coria LM et al. The protein moiety of Brucella abortus outer membrane protein 16 is a new bacterial pathogen-associated molecular pattern that activates dendritic cells in vivo, induces a Th1 immune response, and is a promising self-adjuvanting vaccine against systemic and oral acquired brucellosis. J. Immunol.184, 5200–5212 (2010).
  • Pasquevich KA, Ibanez AE, Coria LM et al. An oral vaccine based on U-Omp19 induces protection against B. abortus mucosal challenge by inducing an adaptive IL-17 immune response in mice. PLoS One6(1), e16203 (2011).
  • Vogel FR. Improving vaccine performance with adjuvants. Clin. Infect. Dis.3, 266–270 (2000).
  • Sala F, Manuela Rigano M, Barbante A et al. Vaccine antigen production in transgenic plants: strategies, gene constructs and perspectives. Vaccine21, 803–808 (2003).
  • Shewen PE, Carrasco-Medina L, McBey BA et al. Challenges in mucosal vaccination of cattle. Vet. Immunol. Immunopathol.128, 192–198 (2009).
  • Feltquate DM, Heaney S, Webster RG et al. Different T helper cell types and antibody isotypes generated by saline and gene gun DNA immunization. J. Immunol.158, 2278–2284 (1997).
  • Pertmer TM, Eisenbraun MD, McCabe D et al. Gene gun-based nucleic acid immunization: elicitation of humoral and cytotoxic T lymphocyte responses following epidermal delivery of nanogram quantities of DNA. Vaccine13, 1427–1430 (1995).
  • Tighe H, Corr M, Roman M et al. Gene vaccination: plasmid DNA is more than just a blueprint. Immunol. Today19, 89–97 (1998).
  • Gurunathan S, Wu CY, Freidag BL et al. DNA vaccines: a key for inducing long-term cellular immunity. Curr. Opin. Immunol.12, 442–447 (2000).
  • Kurar E, Splitter GA. Nucleic acid vaccination of Brucella abortus ribosomal L7/L12 gene elicits immune response. Vaccine15, 1851–1857 (1997).
  • Al-Mariri A, Tibor A, Mertens P et al. Induction of immune response in BALB/c mice with a DNA vaccine encoding bacterioferritin or P39 of Brucella spp. Infect. Immun.69, 6264–6270 (2001).
  • Leclercq SY, Oliveira SC. Protective immunity induced by DNA-library immunization against an intracellular bacterial infection. J. Drug Target11, 531–538 (2003).
  • Leclercq S, Harms JS, Oliveira SC. Enhanced efficacy of DNA vaccines against an intracellular bacterial pathogen by genetic adjuvants. Curr. Pharm. Biotechnol.4, 99–107 (2003).
  • Oñate AA, Cespedes S, Cabrera A et al. A DNA vaccine encoding Cu, Zn superoxide dismutase of Brucella abortus induces protective immunity in BALB/c mice. Infect. Immun.71, 4857–4861 (2003).
  • Munoz-Montesino C, Andrews E, Rivers R et al. 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, 2081–2087 (2004).
  • Cassataro J, Pasquevich KA, Estein SM et al. A DNA vaccine coding for the chimera BLSOmp31 induced a better degree of protection against B. ovis and a similar degree of protection against B. melitensis than Rev.1 vaccination. Vaccine25, 5958–5967 (2007).
  • Cassataro J, Velikovsky CA, de la Barrera S et al. A DNA vaccine coding for the Brucella outer membrane protein 31 confers protection against B. melitensis and B. ovis infection by eliciting a specific cytotoxic response. Infect. Immun.73, 6537–6546 (2005).
  • Schurig GG, Sriranganathan N, Corbel MJ. Brucellosis vaccines: past, present and future. Vet. Microbiol.90, 479–496 (2002).
  • Luo DY, Li P, Xing L et al. DNA vaccine encoding L7/L12-P39 of Brucella abortus induces protective immunity in BALB/c mice. Chin. Med. J. (Engl.)119, 331–334 (2006).
  • Yu DH, Li M, Hu XD et al. A combined DNA vaccine enhances protective immunity against Mycobacterium tuberculosis and Brucella abortus in the presence of an IL-12 expression vector. Vaccine25, 6744–6754 (2007).
  • Yu DH, Hu XD, Cai H. 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, 435–443 (2007).
  • Hu XD, Chen ST, Li JY et al. An IL-15 adjuvant enhances the efficacy of a combined DNA vaccine against Brucella by increasing the CD8+ cytotoxic T cell response. Vaccine28(12), 2408–2415 (2010).
  • Perkins SD, Smither SJ, Atkins HS. Towards a Brucella vaccine for humans. FEMS Microbiol. Rev.34, 379–394 (2010).
  • Ramsay AJ, Kent SJ, Strugnell RA et al. Genetic vaccination strategies for enhanced cellular, humoral and mucosal immunity. Immunol. Rev.171, 27–44 (1999).
  • Gonzalez-Smith A, Vemulapalli R, Andrews E et al. Evaluation of Brucella abortus DNA vaccine by expression of Cu-Zn superoxide dismutase antigen fused to IL-2. Immunobiology211, 65–74 (2006).
  • Singha H, Mallick AI, Jana C et al. Escheriosomes entrapped DNA vaccine co-expressing Cu-Zn superoxide dismutase and IL-18 confers protection against Brucella abortus. Microbes. Infect.10, 1089–1096 (2008).
  • Rosinha GM, Myioshi A, Azevedo V et al. Molecular and immunological characterisation of recombinant Brucella abortus glyceraldehyde-3-phosphate-dehydrogenase, a T- and B-cell reactive protein that induces partial protection when co-administered with an interleukin-12-expressing plasmid in a DNA vaccine formulation. J. Med. Microbiol.51, 661–671 (2002).
  • Commander NJ, Spencer SA, Wren BW et al. The identification of two protective DNA vaccines from a panel of five plasmid constructs encoding Brucella melitensis 16M genes. Vaccine25, 43–54 (2007).
  • Ramshaw IA, Ramsay AJ. The prime–boost strategy: exciting prospects for improved vaccination. Immunol. Today21, 163–165 (2000).
  • Woodland DL. Jump-starting the immune system: prime-boosting comes of age. Trends Immunol.25, 98–104 (2004).
  • Cassataro J, Velikovsky CA, Bruno L et al. Improved immunogenicity of a vaccination regimen combining a DNA vaccine encoding Brucella melitensis outer membrane protein 31 (Omp31) and recombinant Omp31 boosting. Clin. Vaccine Immunol.14, 869–874 (2007).
  • Luo D, Ni B, Li P et al. Protective immunity elicited by a divalent DNA vaccine encoding both the L7/L12 and Omp16 genes of Brucella abortus in BALB/c mice. Infect. Immun.74, 2734–2741 (2006).
  • Gurunathan S, Klinman DM, Seder RA. DNA vaccines: immunology, application, and optimization. Ann. Rev. Immunol.18, 927–974 (2000).
  • Ingolotti M, Kawalekar O, Shedlock DJ et al. DNA vaccines for targeting bacterial infections. Expert Rev. Vaccines9(7), 747–763 (2010).
  • Saez D, Guzman I, Andrews E et al. Evaluation of Brucella abortus DNA and RNA vaccines expressing Cu-Zn superoxide dismutase (SOD) gene in cattle. Vet. Microbiol.129, 396–403 (2008).
  • Kutzler MA, Weiner DB. DNA vaccines: ready for prime time? Nat. Rev. Genet.9(10), 776–788 (2008).
  • Barrio MB, Grilló MJ, Muñoz PM et al. 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. Vaccine27(11), 1741–1749 (2009).
  • González D, Grilló MJ, De Miguel MJ et al. Brucellosis vaccines: assessment of Brucella melitensis lipopolysaccharide rough mutants defective in core and O-polysaccharide synthesis and export. PLoS One3(7), e2760 (2008).
  • Ugalde JE, Comerci DJ, Leguizamón MS et al. Evaluation of Brucella abortus phosphoglucomutase (pgm) mutant as a new live rough-phenotype vaccine. Infect. Immun.71(11), 6264–6269 (2003).
  • Lacerda TL, Cardoso PG, Augusto de Almeida L et al. Inactivation of formyltransferase (wbkC) gene generates a Brucella abortus rough strain that is attenuated in macrophages and in mice. Vaccine28(34), 5627–5634 (2010).
  • Grilló MJ, Manterola L, de Miguel MJ et al. Increases of efficacy as vaccine against Brucella abortus infection in mice by simultaneous inoculation with avirulent smooth bvrS/bvrR and rough wbkA mutants. Vaccine24(15), 2910–2916 (2006).
  • Izadjoo MJ, Bhattacharjee AK, Paranavitana CM et al. Oral vaccination with Brucella melitensis WR201 protects mice against intranasal challenge with virulent Brucella melitensis 16M. Infect. Immun.72(7), 4031–4039 (2004).
  • Izadjoo MJ, Mense MG, Bhattacharjee AK et al. A study on the use of male animal models for developing a live vaccine for brucellosis. Transbound. Emerg. Dis.55(3–4), 145–151 (2008).
  • Tibor A, Jacques I, Guilloteau L et al. Effect of P39 gene deletion in live Brucella vaccine strains on residual virulence and protective activity in mice. Infect. Immun.66(11), 5561–5564 (1998).
  • Kahl-McDonagh MM, Ficht TA. Evaluation of protection afforded by Brucella abortus and Brucella melitensis unmarked deletion mutants exhibiting different rates of clearance in BALB/c mice. Infect. Immun.74(7), 4048–4057 (2006).
  • Rajashekara G, Glover DA, Banai M et al. Attenuated bioluminescent Brucella melitensis mutants GR019 (virB4), GR024 (galE), and GR026 (BMEI1090-BMEI1091) confer protection in mice. Infect. Immun.74(5), 2925–2936 (2006).
  • Arenas-Gamboa AM, Ficht TA, Kahl-McDonagh MM et al. The Brucella abortus S19 DeltavjbR live vaccine candidate is safer than S19 and confers protection against wild-type challenge in BALB/c mice when delivered in a sustained-release vehicle. Infect. Immun.77, 877–884 (2009).
  • Trant CG, Lacerda TL, Carvalho NB et al. 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), 2283–2291 (2010).
  • Cheville NF, Stevens MG, Jensen AE et al. Immune responses and protection against infection and abortion in cattle experimentally vaccinated with mutant strains of Brucella abortus. Am. J. Vet. Res.54(10), 1591–1597 (1993).
  • Fiorentino MA, Campos E, Cravero S et al. Protection levels in vaccinated heifers with experimental vaccines Brucella abortus M1-luc and INTA 2. Vet. Microbiol.132(3–4), 302–311 (2008).
  • Edmonds M, Booth N, Hagius S et al. Attenuation and immunogenicity of a Brucella abortus htrA cycL double mutant in cattle. Vet. Microbiol.76(1), 81–90 (2000).
  • Poester FP, Gonçalves VS, Lage AP. Brucellosis in Brazil. Vet. Microbiol.90(1–4), 55–62 (2002).
  • Samartino LE. Brucellosis in Argentina. Vet. Microbiol.90(1–4), 71–80 (2002).

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