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Protection against virulent Brucella spp. by gamm-airradiated B. ovis in BALB/c mice model

  • Ayman Al-Mariri (Department of Molecular Biology and Biotechnology, Atomic Energy Commission of Syria) ;
  • Laila Al-Hallab (Department of Molecular Biology and Biotechnology, Atomic Energy Commission of Syria) ;
  • Rasha Alabras (Department of Molecular Biology and Biotechnology, Atomic Energy Commission of Syria) ;
  • Heba Kherbik (Department of Molecular Biology and Biotechnology, Atomic Energy Commission of Syria) ;
  • Marwa Khawajkiah (Department of Molecular Biology and Biotechnology, Atomic Energy Commission of Syria)
  • Received : 2021.09.13
  • Accepted : 2021.12.20
  • Published : 2022.01.31

Abstract

Purpose: Brucella spp. is a zoonosis that causes undulant fever in humans and abortion in livestock worldwide. Lately, it was conveyed that vaccines developed by irradiation have induced a strong cellular and humoral immune response which have made these types of vaccines highly effective. Materials and Methods: In this study, we aimed to use the gamma-irradiated B. ovis as a vaccine and to study the humoral immune response and cytokines production in order to evaluate it for protecting mice against B. abortus 544, B. melitensis 16M, and B. ovis. Results: The humoral immune response in immunized mice with gamma-irradiated B. ovis showed a lasting for 8 weeks after immunization. Moreover, immunoglobulin G (IgG), IgG1, IgG2a, and IgG2b isotypes antibodies against B. ovis were observed after 4 and 8 weeks of the last immunization. It was noticed that the production of tumor necrosis factor-α, interferon-γ, and interleukin (IL)-10 continued after 4 and 8 weeks by splenocytes from immunized BALB/c mice, while no production of IL-4 or IL-5 was observed. Conclusion: Our results indicate that the protection of BALB/c mice against B. melitensis 16M, B. abortus 544, and B. ovis was induced and the developed vaccine at our laboratory could stimulate similar protection to those induced by the traditional vaccine.

Keywords

Acknowledgement

The authors would like to express appreciation to Prof. Ibrahim Othman, Director General of the Atomic Energy Commission of Syria for his continuous support, and the Head of the Molecular Biology and Biotechnology Department for their support.

References

  1. Bricker BJ, Ewalt DR, MacMillan AP, Foster G, Brew S. Molecular characterization of Brucella strains isolated from marine mammals. J Clin Microbiol 2000;38:1258-62.
  2. Godfroid J, Garin-Bastuji B, Saegerman C, Blasco JM. Brucellosis in terrestrial wildlife. Rev Sci Tech 2013;32:27-42.
  3. Wareth G, Abdeen A, Ali H, Bardenstein S, et al. Brucellosis in the Mediterranean countries: history, prevalence, distribution, current situation and attempts at surveillance and control. Paris: World Organisation for Animal (OIE); 2019.
  4. Wareth G, Hikal A, Refai M, Melzer F, Roesler U, Neubauer H. Animal brucellosis in Egypt. J Infect Dev Ctries 2014;8:1365-73.
  5. Byndloss MX, Tsolis RM. Brucella spp. virulence factors and immunity. Annu Rev Anim Biosci 2016;4:111-27.
  6. Dorneles EM, de Faria AP, Pauletti RB, et al. Genetic stability of Brucella abortus S19 and RB51 vaccine strains by multiple locus variable number tandem repeat analysis (MLVA16). Vaccine 2013;31:4856-9.
  7. Dadelahi AS, Lacey CA, Chambers CA, Ponzilacqua-Silva B, Skyberg JA. B cells inhibit CD4+ T cell-mediated immunity to brucella infection in a major histocompatibility complex class II-dependent manner. Infect Immun 2020;88:e00075-20.
  8. Goodwin ZI, Pascual DW. Brucellosis vaccines for livestock. Vet Immunol Immunopathol 2016;181:51-8.
  9. Gonzalez D, Grillo 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 One 2008;3:e2760.
  10. Ficht TA, Kahl-McDonagh MM, Arenas-Gamboa AM, Rice-Ficht AC. Brucellosis: the case for live, attenuated vaccines. Vaccine 2009;27(Suppl 4):D40-3.
  11. Schurig GG, Sriranganathan N, Corbel MJ. Brucellosis vaccines: past, present and future. Vet Microbiol 2002;90:479-96.
  12. Clapp B, Skyberg JA, Yang X, Thornburg T, Walters N, Pascual DW. Protective live oral brucellosis vaccines stimulate Th1 and th17 cell responses. Infect Immun 2011;79:4165-74.
  13. Zorgi NE, Costa A, Galisteo AJ Jr, do Nascimento N, de Andrade HF Jr. Humoral responses and immune protection in mice immunized with irradiated T. gondii tachyzoites and challenged with three genetically distinct strains of T. gondii. Immunol Lett 2011;138:187-96.
  14. Seo HS. Application of radiation technology in vaccines development. Clin Exp Vaccine Res 2015;4:145-58.
  15. Sanakkayala N, Sokolovska A, Gulani J, et al. Induction of antigen-specific Th1-type immune responses by gamma-irradiated recombinant Brucella abortus RB51. Clin Diagn Lab Immunol 2005;12:1429-36.
  16. Dabral N, Martha-Moreno-Lafont, Sriranganathan N, Vemulapalli R. Oral immunization of mice with gamma-irradiated Brucella neotomae induces protection against intraperitoneal and intranasal challenge with virulent B. abortus 2308. PLoS One 2014;9:e107180.
  17. Jorge S, Dellagostin OA. The development of veterinary vaccines: a review of traditional methods and modern biotechnology approaches. Biotechnol Res Innov 2017;1:6-13.
  18. Abuhanoglu G, Ozer AY. Radiation sterilization of new drug delivery systems. Interv Med Appl Sci 2014;6:51-60.
  19. Datta SK, Okamoto S, Hayashi T, et al. Vaccination with irradiated Listeria induces protective T cell immunity. Immunity 2006;25:143-52.
  20. Magnani DM, Harms JS, Durward MA, Splitter GA. Non-dividing but metabolically active gamma-irradiated Brucella melitensis is protective against virulent B. melitensis challenge in mice. Infect Immun 2009;77:5181-9.
  21. Surendran N, Hiltbold EM, Heid B, et al. Heat-killed and γ-irradiated Brucella strain RB51 stimulates enhanced dendritic cell activation, but not function compared with the virulent smooth strain 2308. FEMS Immunol Med Microbiol 2010;60:147-55.
  22. Lalsiamthara J, Lee JH. Development and trial of vaccines against Brucella. J Vet Sci 2017;18(S1):281-90.
  23. Lee N, Kim WU. Microbiota in T-cell homeostasis and inflammatory diseases. Exp Mol Med 2017;49:e340.
  24. Sharif MN, Tassiulas I, Hu Y, Mecklenbrauker I, Tarakhovsky A, Ivashkiv LB. IFN-alpha priming results in a gain of pro-inflammatory function by IL-10: implications for systemic lupus erythematosus pathogenesis. J Immunol 2004;172:6476-81.
  25. Moustafa D, Garg VK, Jain N, Sriranganathan N, Vemulapalli R. Immunization of mice with gamma-irradiated Brucella neotomae and its recombinant strains induces protection against virulent B. abortus, B. melitensis, and B. suis challenge. Vaccine 2011;29:784-94.
  26. Salim T, Sershen CL, May EE. Investigating the role of TNF-α and IFN-γ activation on the dynamics of iNOS gene expression in LPS stimulated macrophages. PLoS One 2016;11:e0153289.
  27. Sancho P, Tejedor C, Sidhu-Munoz RS, Fernandez-Lago L, Vizcaino N. Evaluation in mice of Brucella ovis attenuated mutants for use as live vaccines against B. ovis infection. Vet Res 2014;45:61.
  28. Vemulapalli R, He Y, Cravero S, Sriranganathan N, Boyle SM, Schurig GG. Overexpression of protective antigen as a novel approach to enhance vaccine efficacy of Brucella abortus strain RB51. Infect Immun 2000;68:3286-9.
  29. Zhang J, Guo F, Chen C, et al. Brucella melitensis 16MΔhfq attenuation confers protection against wild-type challenge in BALB/c mice. Microbiol Immunol 2013;57:502-10.
  30. Murphy EA, Sathiyaseelan J, Parent MA, Zou B, Baldwin CL. Interferon-gamma is crucial for surviving a Brucella abortus infection in both resistant C57BL/6 and susceptible BALB/c mice. Immunology 2001;103:511-8.
  31. 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 2010;184:5200-12.
  32. Pollak CN, Wanke MM, Estein SM, et al. Immunization with Brucella VirB proteins reduces organ colonization in mice through a Th1-type immune response and elicits a similar immune response in dogs. Clin Vaccine Immunol 2015;22:274-81.
  33. Silva AP, Macedo AA, Silva TM, et al. Protection provided by an encapsulated live attenuated ΔabcBA strain of Brucella ovis against experimental challenge in a murine model. Clin Vaccine Immunol 2015;22:789-97.
  34. Murphy EA, Parent M, Sathiyaseelan J, Jiang X, Baldwin CL. Immune control of Brucella abortus 2308 infections in BALB/c mice. FEMS Immunol Med Microbiol 2001;32:85-8.
  35. 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 2003;71:5750-5.
  36. Grillo MJ, Blasco JM, Gorvel JP, Moriyon I, Moreno E. What have we learned from brucellosis in the mouse model? Vet Res 2012;43:29.
  37. Corsetti PP, de Almeida LA, Carvalho NB, et al. Lack of endogenous IL-10 enhances production of proinflammatory cytokines and leads to Brucella abortus clearance in mice. PLoS One 2013;8:e74729.
  38. Hop HT, Simborio HL, Reyes AW, et al. Immunogenicity and protective effect of recombinant Brucella abortus Ndk (rNdk) against a virulent strain B. abortus 544 infection in BALB/c mice. FEMS Microbiol Lett 2015;362:1-6
  39. Couper KN, Blount DG, Riley EM. IL-10: the master regulator of immunity to infection. J Immunol 2008;180:5771-7.
  40. Avila-Calderon ED, Lopez-Merino A, Sriranganathan N, Boyle SM, Contreras-Rodriguez A. A history of the development of Brucella vaccines. Biomed Res Int 2013;2013:743509.