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Immunization of mice with a novel recombinant molecular chaperon confers protection against Brucella melitensis infection.
Vaccine 32, 6659-6666 (2014)
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.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Brucella ; Molecular Chaperon ; Recombinant Protein ; Vaccine
Language
english
Publication Year
2014
HGF-reported in Year
2014
ISSN (print) / ISBN
0264-410X
e-ISSN
1358-8745
Journal
Vaccine
Quellenangaben
Volume: 32,
Issue: 49,
Pages: 6659-6666
Publisher
Elsevier
Reviewing status
Peer reviewed
Institute(s)
CCG Pediatric Tumor Immunology (AGV-KPT)
POF-Topic(s)
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Research field(s)
Immune Response and Infection
PSP Element(s)
G-520900-001
PubMed ID
25240754
WOS ID
WOS:000345820800013
Erfassungsdatum
2014-09-24