1887

Abstract

attenuated strain RB51 vaccine (RB51) is widely used in prevention of bovine brucellosis. Although vaccination with this strain has been shown to be effective in conferring protection against bovine brucellosis, RB51 has several drawbacks, including residual virulence for animals and humans. Therefore, a safe and efficacious vaccine is needed to overcome these disadvantages. In this study, we constructed several gene deletion mutants (Δ, Δ and Δ single mutants, and ΔΔ and ΔΔ double mutants) of RB51 with the aim of increasing the safety of the possible use of these mutants as vaccine candidates. The RB51Δ, RB51Δ, RB51Δ, RB51ΔΔ and RB51ΔΔ mutants exhibited significant attenuation of virulence when assayed in murine macrophages or in BALB/c mice. A single intraperitoneal immunization with RB51Δ, RB51Δ, RB51ΔΔ or RB51ΔΔ mutants was rapidly cleared from mice within 3 weeks, whereas the RB51Δ mutant and RB51 were detectable in spleens until 4 and 7 weeks, respectively. Vaccination with a single dose of RB51 mutants induced lower protective immunity in mice than did parental RB51. However, a booster dose of these mutants provided significant levels of protection in mice against challenge with either the virulent homologous strain 2308 or the heterologous strain 26. In addition, these mutants were found to induce a mixed but T-helper-1-biased humoral and cellular immune response in immunized mice. These data suggest that immunization with a booster dose of attenuated RB51 mutants provides an attractive strategy to protect against either bovine or canine brucellosis.

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2015-11-01
2024-03-28
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References

  1. Alcantara R.B., Read R.D., Valderas M.W., Brown T.D., Roop R.M. II (2004). Intact purine biosynthesis pathways are required for wild-type virulence of Brucella abortus 2308 in the BALB/c mouse modelInfect Immun 7249114917 [View Article][PubMed]. [Google Scholar]
  2. Arellano-Reynoso B., Díaz-Aparicio E., Leal-Hernández M., Hernández L., Gorvel J.P. (2004). Intracellular trafficking study of a RB51 B. abortus vaccinal strain isolated from cow milkVet Microbiol 98307312 [View Article][PubMed]. [Google Scholar]
  3. 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 challengeInfect Immun 7624482455 [View Article][PubMed]. [Google Scholar]
  4. Ashford D.A., di Pietra J., Lingappa J., Woods C., Noll H., Neville B., Weyant R., Bragg S.L., Spiegel R.A., other authors. (2004). Adverse events in humans associated with accidental exposure to the livestock brucellosis vaccine RB51Vaccine 2234353439 [View Article][PubMed]. [Google Scholar]
  5. Avila-Calderón E.D., Lopez-Merino A., Sriranganathan N., Boyle S.M., Contreras-Rodríguez A. (2013). A history of the development of Brucella vaccinesBioMed Res Int 2013743509 [View Article][PubMed]. [Google Scholar]
  6. Bae D.H., Lee Y.J. (2009). Occurrence of canine brucellosis in Korea and polymorphism of Brucella canis isolates by infrequent restriction site-PCRKorean J Vet Res 49105111. [Google Scholar]
  7. Baek B.K., Lim C.W., Rahman M.S., Kim C.H., Oluoch A., Kakoma I. (2003). Brucella abortus infection in indigenous Korean dogsCan J Vet Res 67312314[PubMed]. [Google Scholar]
  8. Baek B.K., Park M.Y., Islam M.A., Khatun M.M., Lee S.I., Boyle S.M. (2012). The first detection of Brucella canis in cattle in the Republic of KoreaZoonoses Public Health 597782 [View Article][PubMed]. [Google Scholar]
  9. Baldwin C.L., Parent M. (2002). Fundamentals of host immune response against Brucella abortus: what the mouse model has revealed about control of infectionVet Microbiol 90367382 [View Article][PubMed]. [Google Scholar]
  10. 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 buffaloVet Ital 46(13-19), 511[PubMed]. [Google Scholar]
  11. Corbel M.J. (2006). Brucellosis in Humans and AnimalsGenevaWorld Health Organization. [Google Scholar]
  12. Forbes L.B. (1990). Brucella abortus infection in 14 farm dogsJ Am Vet Med Assoc 196911916[PubMed]. [Google Scholar]
  13. Godfroid J., Cloeckaert A., Liautard J.P., Kohler S., Fretin D., Walravens K., Garin-Bastuji B., Letesson J.J. (2005). From the discovery of the Malta fever's agent to the discovery of a marine mammal reservoir, brucellosis has continuously been a re-emerging zoonosisVet Res 36313326 [View Article][PubMed]. [Google Scholar]
  14. Goldman B.S., Gabbert K.K., Kranz R.G. (1996). The temperature-sensitive growth and survival phenotypes of Escherichia coli cydDC and cydAB strains are due to deficiencies in cytochrome bd and are corrected by exogenous catalase and reducing agentsJ Bacteriol 17863486351[PubMed]. [Google Scholar]
  15. Her M., Cho D.H., Kang S.I., Lim J.S., Kim H.J., Cho Y.S., Hwang I.Y., Lee T., Jung S.C., Yoo H.S. (2010). Outbreak of brucellosis in domestic elk in KoreaZoonoses Public Health 57155161 [View Article][PubMed]. [Google Scholar]
  16. Hur J., Baek B.K. (2010). Efficacy of Brucella abortus strain RB51 vaccine in Korean mongrel dogs against virulent strains of B. abortus biotype 1 and B. canisKorean J Vet Serv 332935. [Google Scholar]
  17. Jang Y., Kim H., Bang H.A., Lee M.J., Che N.H., Lee W.C. (2011). Epidemiological aspects of human brucellosis and leptospirosis outbreaks in KoreaJ Clin Med Res 3199202[PubMed]. [Google Scholar]
  18. Jiménez de Bagüés M.P., Elzer P.H., Jones S.M., Blasco J.M., Enright F.M., Schurig G.G., Winter A.J. (1994). Vaccination with Brucella abortus rough mutant RB51 protects BALB/c mice against virulent strains of Brucella abortus, Brucella melitensis, and Brucella ovisInfect Immun 6249904996[PubMed]. [Google Scholar]
  19. Kahl-McDonagh M.M., Ficht T.A. (2006). Evaluation of protection afforded by Brucella abortus and Brucella melitensis unmarked deletion mutants exhibiting different rates of clearance in BALB/c miceInfect Immun 7440484057 [View Article][PubMed]. [Google Scholar]
  20. Kang S.I., Heo E.J., Cho D., Kim J.W., Kim J.Y., Jung S.C., Her M. (2011). Genetic comparison of Brucella canis isolates by the MLVA assay in South KoreaJ Vet Med Sci 73779786 [View Article][PubMed]. [Google Scholar]
  21. Leal-Hernandez M., Díaz-Aparicio E., Pérez R., Andrade L.H., Arellano-Reynoso B., Alfonseca E., Suárez-Güemes F. (2005). Protection of Brucella abortus RB51 revaccinated cows, introduced in a herd with active brucellosis, with presence of atypical humoral responseComp Immunol Microbiol Infect Dis 286370 [View Article][PubMed]. [Google Scholar]
  22. Lee J.J., Simborio H.L., Reyes A.W.B., Kim D.G., Hop H.T., Min W., Her M., Jung S.C., Yoo H.S., Kim S. (2015). Immunoproteomic identification of immunodominant antigens independent of the time of infection in Brucella abortus 2308-challenged cattleVet Res 4617 [View Article][PubMed]. [Google Scholar]
  23. Lucero N.E., Corazza R., Almuzara M.N., Reynes E., Escobar G.I., Boeri E., Ayala S.M. (2010). Human Brucella canis outbreak linked to infection in dogsEpidemiol Infect 138280285 [View Article][PubMed]. [Google Scholar]
  24. McQuiston J.R., Schurig G.G., Sriranganathan N., Boyle S.M. (1995). Transformation of Brucella species with suicide and broad host-range plasmidsMethods Mol Biol 47143148[PubMed]. [Google Scholar]
  25. 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 statusVet Res 35138 [View Article][PubMed]. [Google Scholar]
  26. Olsen S.C., Johnson C.S. (2012). Efficacy of dart or booster vaccination with strain RB51 in protecting bison against experimental Brucella abortus challengeClin Vaccine Immunol 19886890 [View Article][PubMed]. [Google Scholar]
  27. Palmer M.V., Cheville N.F. (1997). Effects of oral or intravenous inoculation with Brucella abortus strain RB51 vaccine in beaglesAm J Vet Res 58851856[PubMed]. [Google Scholar]
  28. Park M.Y., Lee C.S., Choi Y.S., Park S.J., Lee J.S., Lee H.B. (2005). A sporadic outbreak of human brucellosis in KoreaJ Korean Med Sci 20941946 [View Article][PubMed]. [Google Scholar]
  29. Pasquali P., Adone R., Gasbarre L.C., Pistoia C., Ciuchini F. (2001). Mouse cytokine profiles associated with Brucella abortus RB51 vaccination or B. abortus 2308 infectionInfect Immun 6965416544 [View Article][PubMed]. [Google Scholar]
  30. Poole R.K., Gibson F., Wu G. (1994). The cydD gene product, component of a heterodimeric ABC transporter, is required for assembly of periplasmic cytochrome c and of cytochrome bd in Escherichia coliFEMS Microbiol Lett 117217223 [View Article][PubMed]. [Google Scholar]
  31. Schurig G.G., Sriranganathan N., Corbel M.J. (2002). Brucellosis vaccines: past, present and futureVet Microbiol 90479496 [View Article][PubMed]. [Google Scholar]
  32. Seleem M.N., Boyle S.M., Sriranganathan N. (2010). Brucellosis: a re-emerging zoonosisVet Microbiol 140392398 [View Article][PubMed]. [Google Scholar]
  33. Stevens M.G., Olsen S.C., Pugh G.W., Jr, Brees D. (1995). Comparison of immune responses and resistance to brucellosis in mice vaccinated with Brucella abortus 19 or RB51Infect Immun 63264270[PubMed]. [Google Scholar]
  34. 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 miceInfect Immun 7822832291 [View Article][PubMed]. [Google Scholar]
  35. Truong L.Q., Kim J.T., Yoon B.I., Her M., Jung S.C., Hahn T.W. (2011). Epidemiological survey for Brucella in wildlife and stray dogs, a cat and rodents captured on farmsJ Vet Med Sci 7315971601 [View Article][PubMed]. [Google Scholar]
  36. Truong Q.L., Cho Y., Barate A.K., Kim S., Hahn T.W. (2014). Characterization and protective property of Brucella abortus cydC and looP mutantsClin Vaccine Immunol 2115731580 [View Article][PubMed]. [Google Scholar]
  37. Truong Q.L., Cho Y., Barate A.K., Kim S., Watarai M., Hahn T.W. (2015). Mutation of purD and purF genes further attenuates Brucella abortus strain RB51Microb Pathog 7917 [View Article][PubMed]. [Google Scholar]
  38. Wang Z., Wu Q. (2013). Research progress in live attenuated Brucella vaccine developmentCurr Pharm Biotechnol 14887896 [View Article][PubMed]. [Google Scholar]
  39. Wang Z., Niu J., Wang S., Lv Y., Wu Q. (2013). In vivo differences in the virulence, pathogenicity, and induced protective immunity of wboA mutants from genetically different parent Brucella sppClin Vaccine Immunol 20174180 [View Article][PubMed]. [Google Scholar]
  40. Wanke M.M. (2004). Canine brucellosisAnim Reprod Sci 82–83195207 [View Article][PubMed]. [Google Scholar]
  41. Yang X., Thornburg T., Walters N., Pascual D.W. (2010). (znuA(purE Brucella abortus 2308 mutant as a live vaccine candidateVaccine 2810691074 [View Article][PubMed]. [Google Scholar]
  42. Yoon H., Moon O.K., Her M., Carpenter T.E., Kim Y.J., Jung S., Lee S.J. (2010). Impact of bovine brucellosis eradication programs in the Republic of KoreaPrev Vet Med 95288291 [View Article][PubMed]. [Google Scholar]
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