Brucella spp. lumazine synthase as a bovine rotavirus antigen delivery system

Bellido, Demian; Craig, Patricio O.; Mozgovoj, Marina Valeria; Gonzalez, Diego Daniel; Wigdorovitz, Andrés; Goldbaum, Fernando A.; Santos, María José Dus

doi:10.1016/j.vaccine.2008.10.018

Cited by 28 publications

(34 citation statements)

References 53 publications

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“…The other component of the chimera, BLS, was chosen because of its advantages as a carrier for Ag delivery (24)(25)(26). BLS is especially useful because it folds as a dimer of pentamers that share the same C5 symmetry as the pentameric Stx2B Ag.…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

“…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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“…Fusion of the Brucella spp. lumazine synthase (BLS), a highly immunogenic (decameric) protein, with a model virus protein domain (C486 bovine rotavirus VP8 core protein (VP8d)) led to almost 100% protection against homologous challenge with C486 bovine rotavirus [275]. Conjugation of synthetic peptides of influenza virus A M2 extracellular domain with Neisseria meningitidis outer membrane protein complex (OMPC) was able to confer protection against lethal challenge of either H1N1 or H3N1 virus in the presence of Freund's adjuvants in mice [269].…”

Section: Carrier Proteinsmentioning

confidence: 99%

Selection of Adjuvants for Enhanced Vaccine Potency

Wang¹,

Singh²

2011

WJV

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“…Expression and purification of the recombinant proteins have also been reported [22]. Briefly, BLSVP8d and VP8d were expressed as inclusion bodies.…”

Section: Expression and Purification Of Recombinant Proteinsmentioning

confidence: 99%

“…We have previously described the fusion of BLS to the inner domain of the VP8 protein (BLSVP8d) from Bovine Rotavirus (BRV) strain C486. This fusion protein was able to elicit a high antidody response in mice which resulted in fully protection of pups against challenge with virulent C486 BRV [22]. Rotavirus is the major etiological agent of severe neonatal gastroenteritis in mammalian species, including infants and young children worldwide.…”

Section: Introductionmentioning

confidence: 99%

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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Brucella spp. lumazine synthase as a bovine rotavirus antigen delivery system

Cited by 28 publications

References 53 publications

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

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

Selection of Adjuvants for Enhanced Vaccine Potency

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

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