<i>Brucella</i>Lumazine Synthase Elicits a Mixed Th1-Th2 Immune Response and Reduces Infection in Mice Challenged with<i>Brucella abortus</i>544 Independently of the Adjuvant Formulation Used

Velikovsky, Carlos A.; Goldbaum, Fernando A.; Cassataro, Juliana; Estein, Silvia Marcela; Bowden, Robert A.; Bruno, Luciana; Fossati, Carlos A.; Giambartolomei, Guillermo H.

doi:10.1128/iai.71.10.5750-5755.2003

Cited by 88 publications

(71 citation statements)

References 34 publications

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“…Virulent Brucella strain B. abortus 544 and attenuated strain B. abortus RB51, on the basis of which vaccines have been developed (21,36,37), were obtained from the Biology Research Institute (Lanzhou, China). The bacterial cells were grown under aerobic conditions in tryptose-soy broth at 37°C.…”

Section: Methodsmentioning

confidence: 99%

Protective Immunity Elicited by a Divalent DNA Vaccine Encoding Both the L7/L12 and Omp16 Genes ofBrucella abortusin BALB/c Mice

Luo

et al. 2006

Infect Immun

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This study was designed to evaluate the immunogenicity and the protective efficacy of a divalent fusion DNA vaccine encoding both the Brucella abortus L7/L12 protein (ribosomal protein) and Omp16 protein (outer membrane lipoprotein), designated pcDNA3.1-L7/L12-Omp16. Intramuscular injection of this divalent DNA vaccine into BALB/c mice elicited markedly both humoral and cellular immune responses. The specific antibodies exhibited a dominance of immunoglobulin G2a (IgG2a) over IgG1. In addition, the dual-gene DNA vaccine elicited a strong T-cell proliferative response and induced a large amount of gamma interferonproducing T cells upon restimulation in vitro with recombinant fusion protein L7/L12-Omp16, suggesting the induction of a typical T-helper-1-dominated immune response in vivo. This divalent DNA vaccine could also induce a significant level of protection against challenge with the virulent strain B. abortus 544 in BALB/c mice. Furthermore, the protection level induced by the divalent DNA vaccine was significantly higher than that induced by the univalent DNA vaccines pcDNA3.1-L7/L12 or pcDNA3.1-Omp16. Taken together, the results of this study verify for the first time that the Omp16 gene can be a candidate target for a DNA vaccine against brucellosis. Additionally, a divalent genetic vaccine based on the L7/L12 and Omp16 genes can elicit a stronger cellular immune response and better immunoprotection than the relevant univalent vaccines can.Brucella abortus is a facultative intracellular pathogen and one of the etiological agents of brucellosis that can infect humans and domestic animals (11). Like other intracellular bacterial pathogens, the host resistance to B. abortus depends mainly on acquired cell-mediated immunity (CMI) (40). The development of a Th1 subset of CD4 ϩ lymphocytes secreting gamma interferon (IFN-␥), a crucial cytokine that can upregulate the anti-Brucella activity of macrophages (14), and the development of CD8 ϩ T lymphocytes secreting IFN-␥ and lysing Brucella-infected cells (24) are the two main components of the protective response of the infected hosts. Live attenuated vaccines that can stimulate strong CMI responses are usually very effective against brucellosis. Attenuated strains such as Brucella melitensis Rev1 and B. abortus S19 and RB51 are being used to control brucellosis in domestic animals (21). However, no safe, effective vaccine is available for human use. The vaccine strains used for animals are considered too virulent; thus, they are not safe for human use. A vaccine that will be noninfectious to humans but effective in stimulating a broad protective immune response is needed to control brucellosis. To develop this type of Brucella vaccine, several research groups are pursuing different strategies, including development of subunit vaccines (25), utilization of bacterial vectors (28), and overexpression of protective homologous antigen (38).Another new strategy for developing safe and efficacious vaccines is immunization with plasmid DNA encoding the protective antig...

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Section: Methodsmentioning

confidence: 99%

Protective Immunity Elicited by a Divalent DNA Vaccine Encoding Both the L7/L12 and Omp16 Genes ofBrucella abortusin BALB/c Mice

Luo

et al. 2006

Infect Immun

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“…The enzyme lumazine synthase from Brucella spp. (BLS) is a highly immunogenic and stable dimer of pentamers and a scaffold with enormous plasticity on which to display foreign Ags (22)(23)(24)(25)(26). The N terminal of each monomer would be displayed at the vertices of a symmetric pentamer at a distance of 40 Å .…”

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confidence: 99%

Immunization with a Chimera Consisting of the B Subunit of Shiga Toxin Type 2 and Brucella Lumazine Synthase Confers Total Protection against Shiga Toxins in Mice

Mejias

Ghersi²,

Craig

et al. 2013

The Journal of Immunology

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The striking feature of enterohemorrhagic Escherichia coli (EHEC) infections is the production of Shiga toxins (Stx) implicated in the development of the life-threatening hemolytic uremic syndrome. Despite the magnitude of the social impact of EHEC infections, no licensed vaccine or effective therapy is available for human use. One of the biggest challenges is to develop an effective and safe immunogen to ensure nontoxicity, as well as a strong input to the immune system to induce long-lasting, high-affinity Abs with anti-Stx–neutralizing capacity. The enzyme lumazine synthase from Brucella spp. (BLS) is a highly stable dimer of pentamers and a scaffold with enormous plasticity on which to display foreign Ags. Taking into account the advantages of BLS and the potential capacity of the B subunit of Stx2 to induce Abs that prevent Stx2 toxicity by blocking its entrance into the host cells, we engineered a new immunogen by inserting the B subunit of Stx2 at the amino termini of BLS. The resulting chimera demonstrated a strong capacity to induce a long-lasting humoral immune response in mice. The chimera induced Abs with high neutralizing capacity for Stx2 and its variants. Moreover, immunized mice were completely protected against i.v. Stx2 challenge, and weaned mice receiving an oral challenge with EHEC were completely protected by the transference of immune sera. We conclude that this novel immunogen represents a promising candidate for vaccine or Ab development with preventive or therapeutic ends, for use in hemolytic uremic syndrome–endemic areas or during future outbreaks caused by pathogenic strains of Stx-producing E. coli.

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“…For example, BLS can induce a strong signal transduction mediated by B-cell receptors and it also activates the cellular response by delivering CD8+ T-cell epitopes into the MHC class I pathway. Moreover, BLS also activates and induces the proliferation of dendritic cells via TLR4 [37,38]. In this work, hens immunized with BLSVP8d developed high titers of antibodies, even using low amounts of the antigen.…”

Section: Resultsmentioning

confidence: 82%

Brucella spp. Lumazine synthase as a novel immunomodulator to produce egg yolk antibodies

Bellido¹,

Chacana²,

Mozgovoj³

et al. 2012

ABB

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Lumazine synthase from Brucella spp. (BLS) is a highly immunogenic decameric protein. It has been previously described as a carrier of peptides or proteins to increase their immunogenicity in different animal species, but its activity has never been evaluated in chickens. In this work, the use of BLS to improve the antibody response against bovine rotavirus (BRV) VP8d protein in laying hens was assessed. VP8d is the inner domain of the VP8 spike protein which preserves the sialic acid binding activity and the neutralizing epitopes present in the viral protein.Hens were immunized three times with 2 μg of VP8d alone or fused to BLS. Hens inoculated with BLSVP8d developed higher antibody titers (evaluated by ELISA and viral neutralization test) than hens immunized either with VP8d alone or the mixture of VP8d and BLS. Furthermore, IgY antibodies against BLSVP8d were able to fully protect mice against challenge with virulent BRV in a dose-depent-manner. Overall, these results demonstrate that BLS is a potent immonumodulator that enhances the antibody response in hens, thus increasing the concentration of specific IgY in the egg yolk, one of the main issues to be adressed in order to improve the use of the IgY technology.

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BrucellaLumazine Synthase Elicits a Mixed Th1-Th2 Immune Response and Reduces Infection in Mice Challenged withBrucella abortus544 Independently of the Adjuvant Formulation Used

Cited by 88 publications

References 34 publications

Protective Immunity Elicited by a Divalent DNA Vaccine Encoding Both the L7/L12 and Omp16 Genes ofBrucella abortusin BALB/c Mice

Protective Immunity Elicited by a Divalent DNA Vaccine Encoding Both the L7/L12 and Omp16 Genes ofBrucella abortusin BALB/c Mice

Immunization with a Chimera Consisting of the B Subunit of Shiga Toxin Type 2 and Brucella Lumazine Synthase Confers Total Protection against Shiga Toxins in Mice

Brucella spp. Lumazine synthase as a novel immunomodulator to produce egg yolk antibodies

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