A DNA Vaccine Coding for theBrucellaOuter Membrane Protein 31 Confers Protection againstB. melitensisandB. ovisInfection by Eliciting a Specific Cytotoxic Response

Cassataro, Juliana; Velikovsky, Carlos A.; Barrera, Silvia de la; Estein, Silvia Marcela; Bruno, Luciana; Bowden, Robert A.; Pasquevich, Karina A.; Fossati, Carlos A.; Giambartolomei, Guillermo H.

doi:10.1128/iai.73.10.6537-6546.2005

Cited by 103 publications

(75 citation statements)

References 57 publications

(67 reference statements)

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“…Conversely, against smooth B. melitensis, the most virulent strain of Brucella spp., the only protective Ag identified was the 31-kDa outer membrane protein (Omp) of Brucella delivered as a DNA vaccine (11). However, repeated doses and high concentrations of the plasmid containing the Omp31 gene are needed to generate an efficacious response (11), probably because of the low in vivo transfection efficiency for this type of plasmid vector (24,25,40).…”

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confidence: 99%

Vaccination with the RecombinantBrucellaOuter Membrane Protein 31 or a Derived 27-Amino-Acid Synthetic Peptide Elicits a CD4⁺T Helper 1 Response That Protects againstBrucella melitensisInfection

et al. 2005

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The immunogenicity and protective efficacy of the recombinant 31-kDa outer membrane protein from Brucella melitensis (rOmp31), administered with incomplete Freund's adjuvant, were evaluated in mice. Immunization of BALB/c mice with rOmp31 conferred protection against B. ovis and B. melitensis infection. rOmp31 induced a vigorous immunoglobulin G (IgG) response, with higher IgG1 than IgG2 titers. In addition, spleen cells from rOmp31-immunized mice produced interleukin 2 (IL-2) and gamma interferon, but not IL-10 or IL-4, after in vitro stimulation with rOmp31, suggesting the induction of a T helper 1 (Th1) response. Splenocytes from rOmp31-vaccinated animals also induced a specific cytotoxic-T-lymphocyte activity, which led to the in vitro lysis of Brucella-infected macrophages. In vitro T-cell subset depletion indicated that rOmp31 immunization elicited specific CD4 ؉ T cells that secrete IL-2 and gamma interferon, while CD8 ؉ T cells induced cytotoxic-T-lymphocyte activity. In vivo depletion of T-cell subsets showed that the rOmp31-elicited protection against B. melitensis infection is mediated by CD4 ؉ T cells while the contribution of CD8 ؉ T cells may be limited. We then evaluated the immunogenicity and protective efficacy of a known exposed region from Omp31 on the Brucella membrane, a peptide that contains amino acids 48 to 74 of Omp31. Immunization with the synthetic peptide in adjuvant did not elicit a specific humoral response but elicited a Th1 response mediated by CD4 ؉ T cells. The peptide in adjuvant induced levels of protection similar to those induced by rOmp31 against B. melitensis but less protection than was induced by rOmp31 against B. ovis. Our results indicate that rOmp31 could be a useful candidate for the development of subunit vaccines against B. melitensis and B. ovis.Brucellae are gram-negative, facultative intracellular pathogens that may cause severe disease in both humans and animals. Brucellosis remains endemic in many developing countries, causing important economic losses (31). Brucella melitensis is the most pathogenic species for humans and may cause abortions in sheep, goats, and cows. Vaccination of sheep and goats against B. melitensis with live attenuated smooth B. melitensis Rev.

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Vaccination with the RecombinantBrucellaOuter Membrane Protein 31 or a Derived 27-Amino-Acid Synthetic Peptide Elicits a CD4⁺T Helper 1 Response That Protects againstBrucella melitensisInfection

et al. 2005

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“…This does not necessarily suggest that pCMVbp26 and pCMVTF vaccines are poor immunogens because many investigators have also demonstrated weak antibody responses following DNA vaccination of mice (Cassataro et al, 2005;Gonzalez-Smith et al, 2006). Rather, antibody responses are generally suboptimal following DNA vaccination, often requiring a protein boost or, alternatively, they may be in part attributed to the dampening effect by Th1 cell bias used by this immunization method (Commander et al, 2007).…”

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confidence: 95%

DNA VACCINATION OF BISON TO BRUCELLAR ANTIGENS ELICITS ELEVATED ANTIBODY AND IFN-γ RESPONSES

Clapp

Walters

Thornburg

et al. 2011

Journal of Wildlife Diseases

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ABSTRACT:Brucella abortus remains a threat to the health and well-being of livestock in states bordering the Greater Yellowstone Area. During the past several years, cohabitation of infected wildlife with cattle has jeopardized the brucellosis-free status of Idaho, USA; Wyoming, USA; and Montana, USA. Current livestock B. abortus vaccines have not proven to be efficacious in bison (Bison bison) or elk (Cervus elaphus nelsoni). One problem with the lack of vaccine efficacy may stem from the failure to understand wildlife immune responses to vaccines. In an attempt to understand their immune responses, bison were vaccinated with eukaryotic DNA expression vectors encoding the Brucella periplasmic protein, bp26, and the chaperone protein, trigger factor (TF). These DNA vaccines have previously been shown to be protective against Brucella infection in mice. Bison were immunized intramuscularly at weeks 0, 2, and 4 with bp26 and TF DNA vaccines plus CpG adjuvant or empty vector (control) plus CpG. Blood samples were collected before vaccination and at 8, 10, and 12 wk after primary vaccination. The results showed that bison immunized with bp26 and TF DNA vaccines developed enhanced antibody, proliferative T cell, and interferon-gamma (IFN-c) responses upon in vitro restimulation with purified recombinant bp26 or TF antigens, unlike bison immunized with empty vector. Flow cytometric analysis revealed that the percentages of CD4 + and CD8 + T lymphocytes from the DNA-vaccinated groups were significantly greater than they were for those bison given empty vector. These data suggest that DNA vaccination of bison may elicit strong cellular immune responses and serve as an alternative for vaccination of bison for brucellosis.

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“…Inoculation with plasmid DNAs expressing foreign proteins stimulates both cellular and humoral immune responses that protect against bacteria, parasites, viruses, and tumors [20], and is a reasonably powerful and novel technique of immunization [21]. The aim of the present study is to investigate the immunogenicity and protective capacity of a DNA vaccine encoding the eae and omp31 proteins of E. coli and B. melitensis, respectively.…”

Section: Introductionmentioning

confidence: 99%

Induction of protective immune responses in mice by double DNA vaccine encoding of Brucella melitensis Omp31 and Escherichia coli Eae genes

Ranjbar¹,

Sharifimoghadam²,

Saeidi³

et al. 2016

Trop. J. Pharm Res

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A DNA Vaccine Coding for theBrucellaOuter Membrane Protein 31 Confers Protection againstB. melitensisandB. ovisInfection by Eliciting a Specific Cytotoxic Response

Cited by 103 publications

References 57 publications

Vaccination with the RecombinantBrucellaOuter Membrane Protein 31 or a Derived 27-Amino-Acid Synthetic Peptide Elicits a CD4⁺T Helper 1 Response That Protects againstBrucella melitensisInfection

Vaccination with the RecombinantBrucellaOuter Membrane Protein 31 or a Derived 27-Amino-Acid Synthetic Peptide Elicits a CD4⁺T Helper 1 Response That Protects againstBrucella melitensisInfection

DNA VACCINATION OF BISON TO BRUCELLAR ANTIGENS ELICITS ELEVATED ANTIBODY AND IFN-γ RESPONSES

Induction of protective immune responses in mice by double DNA vaccine encoding of <i>Brucella melitensis</i> Omp31 and <i>Escherichia coli</i> Eae genes

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A DNA Vaccine Coding for theBrucellaOuter Membrane Protein 31 Confers Protection againstB. melitensisandB. ovisInfection by Eliciting a Specific Cytotoxic Response

Cited by 103 publications

References 57 publications

Vaccination with the RecombinantBrucellaOuter Membrane Protein 31 or a Derived 27-Amino-Acid Synthetic Peptide Elicits a CD4+T Helper 1 Response That Protects againstBrucella melitensisInfection

Vaccination with the RecombinantBrucellaOuter Membrane Protein 31 or a Derived 27-Amino-Acid Synthetic Peptide Elicits a CD4+T Helper 1 Response That Protects againstBrucella melitensisInfection

DNA VACCINATION OF BISON TO BRUCELLAR ANTIGENS ELICITS ELEVATED ANTIBODY AND IFN-γ RESPONSES

Induction of protective immune responses in mice by double DNA vaccine encoding of <i>Brucella melitensis</i> Omp31 and <i>Escherichia coli</i> Eae genes

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Vaccination with the RecombinantBrucellaOuter Membrane Protein 31 or a Derived 27-Amino-Acid Synthetic Peptide Elicits a CD4⁺T Helper 1 Response That Protects againstBrucella melitensisInfection

Vaccination with the RecombinantBrucellaOuter Membrane Protein 31 or a Derived 27-Amino-Acid Synthetic Peptide Elicits a CD4⁺T Helper 1 Response That Protects againstBrucella melitensisInfection