Immune Modulation of Recombinant OmpA against Brucella abortus 544 Infection in Mice
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Brucellosis affects a wide range of host species, including humans and many livestock animals. Chronic infections of the disease make antibiotic treatment costly, and the current vaccine used in livestock has not been approved for human use. This study investigated the possible use of the Brucella abortus outer membrane protein A (OmpA) as a candidate subunit vaccine in an infected mouse model. The ompA gene was cloned and overexpressed, and the recombinant OmpA (rOmpA) protein fused to maltose binding protein (MBP) was purified in Escherichia coli. Immunogenicity was verified through western blotting, and mice were immunized and challenged to evaluate its protective effect. Mice treated with rOmpA exhibited induced humoral and host cell-mediated responses, with a significant increase in immunoglobulin G (IgG1 and IgG2a) and cytokine levels, especially TNF-α and IL-12, compared with the control groups treated with either MBP or PBS. In conclusion, rOmpA should be highly considered as a future subunit vaccine for brucellosis, and further studies regarding rOmpA and its protective ability are suggested.
Abstract
Brucellosis affects a wide range of host species, including humans and many livestock animals. Chronic infections of the disease make antibiotic treatment costly, and the current vaccine used in livestock has not been approved for human use. This study investigated the possible use of the Brucella abortus outer membrane protein A (OmpA) as a candidate subunit vaccine in an infected mouse model. The ompA gene was cloned and overexpressed, and the recombinant OmpA (rOmpA) protein fused to maltose binding protein (MBP) was purified in Escherichia coli. Immunogenicity was verified through western blotting, and mice were immunized and challenged to evaluate its protective effect. Mice treated with rOmpA exhibited induced humoral and host cell-mediated responses, with a significant increase in immunoglobulin G (IgG1 and IgG2a) and cytokine levels, especially TNF-α and IL-12, compared with the control groups treated with either MBP or PBS. In conclusion, rOmpA should be highly considered as a future subunit vaccine for brucellosis, and further studies regarding rOmpA and its protective ability are suggested.
참고문헌 (35)
- Acha PN, "Zoonoses and Communicable Disease Common to Man and Animals. Vol. 1", pp.40~67 (2003), Pan American Health Organization
- Akova M, "Quinolones in treatment of human brucellosis:comparative trial of ofloxacin-rifampin versus doxycyclinerifampin", Antimicrob. Agents Chemother, 37, pp.1831~1834 (1993)
- Al-Mariri A, "Protection of BALB", c mice against Brucella abortus 544 challenge by vaccination with bacterioferritin or P39 recombinant proteins with CpG oligodeoxynucleotides as adjuvants, 2001, pp.69, 4816~4822
- Athanassakis I, "Cytokine production in the serum and spleen of mice from day 6 to 14 of gestation:cytokines", placenta, serum, pp.Dev. Immunol, 1996[DOI]
- Aygen B, "Clinical manifestations, complications and treatment of brucellosis: a retrospective evaluation of 480 patients", Méd. Mal. Infect, 32, pp.485~493 (2002)
- Barrionuevo P, "Brucella abortus inhibits major histocompatibility complex III expression and antigen processing through interleukin-6 secretion via Toll-like receptor 2", Infect. Immun, 76, pp.250~262 (2008)
- Cassataro J, "Vaccination with the recombinant Brucella outer membrane protein 31 or a derived 27-amino-acid synthetic peptide against Brucella melitensis infection", Infect. Immun, 73, pp.8079~8088 (2005)
- Corbel MJ, "Recent advances in brucellosis", J. Med. Microbiol, 46, pp.101~103 (1997)
- Dabo SM, "Vaccination with Pasteurella multocida recombinant OmpA induces strong but non-protective and deleterious Th2-type immune response in mice", Vaccine, 26, pp.4345~4351 (2008)
- Delpino MV, "Vaccination with Brucella recombinant DnaK and SurA proteins induces protection against Brucella abortus infection in BALB", c mice, 2007, pp.25, 6721~6729
- Eskra L, "Brucella abortus genes identified following constitutive growth and macrophage infection", Infect. Immun, 69, pp.7736~7742 (2001)
- Ficht TA, "Brucellosis: the case for live, attenuated vaccines", Vaccine, 27, pp.40~43 (2009)
- Huang LY, "Heat-killed Brucella abortus induces TNF and IL-12p40 by distinct MyD88-dependent pathways: TNF, unlike IL-12p40 secretion, is Toll-like receptor 2 dependent", J. Immun, 171, pp.1441~1446 (2003)
- Jeannin P, "OmpA targets dendritic cells, induces their maturation and delivers antigen into the MHC class I presentation pathway", Nat. Immunol, 1, pp.502~509 (2000)
- Jimenez de Bagues MP, "The Brucella abortus RB51 vaccine does not confer protection against Brucella ovis in rams", Vaccine, 13, pp.301~304 (1995)
- Kaushik P, "Protection of mice against Brucella abortus 544 challenge by vaccination with recombinant OMP28 adjuvanted with CpG oligonucleotides", Vet. Res. Commun, 34, pp.119~132 (2010)
- Leclerq S, "Induction of a Th1-type of immune respose but not protective immunity by intramuscular DNA immunization with Brucella abortus GroEL heat-shock gene", J. Med. Microbiol, 51, pp.20~26 (2002)
- Lee JJ, "Characterization of culture supernatant proteins from Brucella abortus and its protection effects against murine brucellosis", Comp. Immunol. Microbiol. Infect. Dis, 37, pp.221~228 (2014)
- Lim JJ, "Evaluation of recombinant 28 kDa outer membrane protein of Brucella abortus for the clinical diagnosis of bovine brucellosis in Korea", J. Vet. Med. Sci, 74, pp.687~691 (2012)
- Lin J, "Outer membrane proteins:key players for bacterial adaptation in host niches", Microbes Infect, 4, pp.325~331 (2002)
- Lin L, "Acinetobacter baumannii rOmpA vaccine dose alters immune polarization and immunodominant epitopes", Vaccine, 31, pp.313~318 (2013)
- Lindler LE, "Cloning of Brucella melitensis group 3antigen gene encoding Omp28, a protein recognized by the humoral immune response during human brucellosis", Infect. Immun, 64, pp.2490~2499 (1996)
- Lubroth J, "Veterinary vaccine and their use in developing countries", Rev. Sci. Tech, 26, pp.179~201 (2007)
- Macedo GC, "Central role of MyD88-dependent dendritic cell maturation and proinflammatory cytokine production to control Brucella abortus infection", J. Immunol, 180, pp.1080~1087 (2008)
- Makidon PE, "Induction of immune response to t he 1 7 kD a OMPA Burkholderia cenocepacia polypeptide and protection against pulmonary infection in mice after nasal vaccination with an OMP nanoemulsion-based vaccine", Med. Microbiol. Immunol, 199, pp.81~92 (2010)
- Moriyón I, "Structure and properties of the outer membranes of Brucella abortus and Brucella melitensis", Int. Microbiol, 1, pp.19~26 (1998)
- Nicoletti PL, "A short history of brucellosis", Vet. Microbiol, 90, pp.5~9 (2002)
- Oliveira SC, "Immunization of mice with recombinant L7", L12 ribosomal protein confers protection against Brucella abortus infection, 1996, pp.14, 959~962
- Onate AA, "A DNA vaccine encoding Cu,Zn superoxide dismutase of Brucella abortus induces protective immunity in BALB", c mice, 2003, pp.71, 4857~4861
- Pasquevich KA, "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, pp.436~445 (2009)
- Pore D, "Outer membrane protein (OmpA) of Shigella flexneri 2a, induces protective immune response in a mouse model", PLoS One, 6, pp.e22663~ (2011)
- Ragan VE, "The animal and plant health inspection service (APHIS) brucellosis eradication program in the United States", Vet. Microbiol, 90, pp.11~18 (2002)
- Schurig GG, "Brucellosis vaccines: past, present and future", Vet. Microbiol, 90, pp.479~496 (2002)
- Soulas C, "Outer membrane protein A (OmpA)binds to and activates human macrophages", J. Immun, 165, pp.2335~2340 (2000)
- Zhan Y, "Tumor necrosis factor alpha and interleukin-12 contribute to resistance to the intracellular bacterium Brucella abortus by different mechanisims", Infect. Immun, 64, pp.2782~2786 (1996)
