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Immunization of mice with a novel recombinant molecular chaperon confers protection against Brucella melitensis infection.
Vaccine 2014; 32(49):6659-66V

Abstract

Brucella spp. are zoonotic Gram-negative intracellular pathogens with the ability to survive and replicate in phagocytes. It has been shown that bacterial proteins expressed abundantly in this niche are stress-related proteins capable of triggering effective immune responses. BMEI1549 is a molecular chaperone designated DnaK that is expressed under stress conditions and helps to prevent formation of protein aggregates. In order to study the potential of DnaK as a prospective Brucella subunit vaccine, immunogenicity and protective efficacy of recombinant DnaK from Brucella melitensis was evaluated in BALB/c mice. The dnak gene was cloned, expressed in Escherichia coli, and the resulting recombinant protein used as subunit vaccine. DnaK-immunized mice showed a strong lymphocyte proliferative response to in vitro antigen stimulation. Although comparable levels of antigen-specific IgG2a and IgG1 were observed in immunized mice, high amounts of IFN-γ, IL-12 and IL-6, no detectable level of IL-4 and very low levels of IL-10 and IL-5 were produced by splenocytes of vaccinated mice suggesting induction of a Th1 dominant immune response by DnaK. Compared to control animals, mice vaccinated with DnaK exhibited a significant degree of protection against subsequent Brucella infection (p<0.001), albeit this protection was less than the protection conferred by Rev.1 (p<0.05). A further increase in protection was observed, when DnaK was combined with recombinant Omp31. Notably, this combination, as opposed to each component alone, induced statistically similar level of protection as induced by Rev.1 suggesting that DnaK could be viewed as a promising candidate for the development of a subunit vaccine against brucellosis.

Authors+Show Affiliations

Department of Microbiology and Immunology, Faculty of Medicine, Kashan University of Medical Sciences, Kashan, Iran.Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR, Tehran, Iran. Electronic address: Mahjed@avicenna.ac.ir.Technische Universität München & Helmholtz Zentrum München, Munich, Germany.Department of Pathobiology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.Nanobiotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran; Immunology Research Center, Iran University of Medical Sciences, Tehran, Iran. Electronic address: zarnani@avicenna.ac.ir.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25240754

Citation

Ghasemi, Amir, et al. "Immunization of Mice With a Novel Recombinant Molecular Chaperon Confers Protection Against Brucella Melitensis Infection." Vaccine, vol. 32, no. 49, 2014, pp. 6659-66.
Ghasemi A, Jeddi-Tehrani M, Mautner J, et al. Immunization of mice with a novel recombinant molecular chaperon confers protection against Brucella melitensis infection. Vaccine. 2014;32(49):6659-66.
Ghasemi, A., Jeddi-Tehrani, M., Mautner, J., Salari, M. H., & Zarnani, A. H. (2014). Immunization of mice with a novel recombinant molecular chaperon confers protection against Brucella melitensis infection. Vaccine, 32(49), pp. 6659-66. doi:10.1016/j.vaccine.2014.09.013.
Ghasemi A, et al. Immunization of Mice With a Novel Recombinant Molecular Chaperon Confers Protection Against Brucella Melitensis Infection. Vaccine. 2014 Nov 20;32(49):6659-66. PubMed PMID: 25240754.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Immunization of mice with a novel recombinant molecular chaperon confers protection against Brucella melitensis infection. AU - Ghasemi,Amir, AU - Jeddi-Tehrani,Mahmood, AU - Mautner,Josef, AU - Salari,Mohammad Hossein, AU - Zarnani,Amir-Hassan, Y1 - 2014/09/19/ PY - 2014/06/24/received PY - 2014/09/04/revised PY - 2014/09/05/accepted PY - 2014/9/22/entrez PY - 2014/9/23/pubmed PY - 2015/7/18/medline KW - Brucella KW - Molecular chaperon KW - Recombinant protein KW - Vaccine SP - 6659 EP - 66 JF - Vaccine JO - Vaccine VL - 32 IS - 49 N2 - Brucella spp. are zoonotic Gram-negative intracellular pathogens with the ability to survive and replicate in phagocytes. It has been shown that bacterial proteins expressed abundantly in this niche are stress-related proteins capable of triggering effective immune responses. BMEI1549 is a molecular chaperone designated DnaK that is expressed under stress conditions and helps to prevent formation of protein aggregates. In order to study the potential of DnaK as a prospective Brucella subunit vaccine, immunogenicity and protective efficacy of recombinant DnaK from Brucella melitensis was evaluated in BALB/c mice. The dnak gene was cloned, expressed in Escherichia coli, and the resulting recombinant protein used as subunit vaccine. DnaK-immunized mice showed a strong lymphocyte proliferative response to in vitro antigen stimulation. Although comparable levels of antigen-specific IgG2a and IgG1 were observed in immunized mice, high amounts of IFN-γ, IL-12 and IL-6, no detectable level of IL-4 and very low levels of IL-10 and IL-5 were produced by splenocytes of vaccinated mice suggesting induction of a Th1 dominant immune response by DnaK. Compared to control animals, mice vaccinated with DnaK exhibited a significant degree of protection against subsequent Brucella infection (p<0.001), albeit this protection was less than the protection conferred by Rev.1 (p<0.05). A further increase in protection was observed, when DnaK was combined with recombinant Omp31. Notably, this combination, as opposed to each component alone, induced statistically similar level of protection as induced by Rev.1 suggesting that DnaK could be viewed as a promising candidate for the development of a subunit vaccine against brucellosis. SN - 1873-2518 UR - https://www.unboundmedicine.com/medline/citation/25240754/Immunization_of_mice_with_a_novel_recombinant_molecular_chaperon_confers_protection_against_Brucella_melitensis_infection_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0264-410X(14)01260-2 DB - PRIME DP - Unbound Medicine ER -