Immunization with Recombinant
 Brucella
 Species Outer Membrane Protein Omp16 or Omp19 in Adjuvant Induces Specific CD4
 +
 and CD8
 +
 T Cells as Well as Systemic and Oral Protection against
 Brucella abortus
 Infection

Pasquevich, KA; Estein, SM; García, Cristina; Zwerdling, Astrid; Coria, LM; Barrionuevo, Paula; Ca, Fossati; Gh, Giambartolomei; Cassataro, Juliana

doi:10.1128/iai.00123-09

Cited by 24 publications

(39 citation statements)

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“…Several past (21) and more recent studies (18,80,81) + memory T cells in the absence of MHC-II-dependent Agpresenting pathways. We previously observed during the Brucella primary response that in absence of MHC-II, IFN-gproducing CD8…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, the vast majority of publications reports only the protective ability of candidate vaccines, limiting their analysis to present CFU counts in the spleen after challenge (14,15). Evaluations of the ability of vaccines to induce IFN-g-producing cells, detected in vitro after restimulation, and/or a humoral response are also often reported (16)(17)(18). Rare studies (19)(20)(21)(22) have tried to characterize the nature of the protective immune response induced by vaccination and thus identify potential protective immune markers for the development of a rational strategy to select candidate vaccines.…”

mentioning

confidence: 99%

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Humoral Immunity and CD4+ Th1 Cells Are Both Necessary for a Fully Protective Immune Response upon Secondary Infection with Brucella melitensis

Vitry

Mambres

Trez

et al. 2014

The Journal of Immunology

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Brucella spp are intracellular bacteria that cause brucellosis, one of the most common zoonoses in the world. Given the serious medical consequences of this disease, a safe and effective human vaccine is urgently needed. Efforts to develop this vaccine have been hampered by our lack of understanding of what constitutes a protective memory response against Brucella. In this study, we characterize the cells and signaling pathways implicated in the generation of a protective immune memory response following priming by the injection of heat-killed or live Brucella melitensis 16M. Using a panel of gene-deficient mice, we demonstrated that during a secondary recall response, both the Brucella-specific humoral response and CD4+ Th1 cells must act together to confer protective immunity in the spleen to B. melitensis infection. Humoral protective immunity is induced by the inoculation of both heat-killed and live bacteria, and its development does not require T cells, MyD88/IL-12p35 signaling pathways, or an activation-induced deaminase–mediated isotype switch. In striking contrast, the presence of memory IFN-γ–producing CD4+ Th1 cells requires the administration of live bacteria and functional MyD88/IL-12p35 pathways. In summary, our work identifies several immune markers closely associated with protective immune memory and could help to define a rational strategy to obtain an effective human vaccine against brucellosis.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Humoral Immunity and CD4+ Th1 Cells Are Both Necessary for a Fully Protective Immune Response upon Secondary Infection with Brucella melitensis

Vitry

Mambres

Trez

et al. 2014

The Journal of Immunology

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“…This pathway is referred to as the cytosolic pathway and predominates in vivo. The degradative potential of lysosomes influences the amount of Ag that can reach the cytoplasm (10,18 (19,20). We have demonstrated that U-Omp19 is a protein with self-adjuvanting capacity, because oral or systemic immunization with U-Omp19 (produced either in Escherichia coli or in plants) without adjuvants conferred significant protection against oral or systemic B. abortus infection and induced a Th 1 response independent of TLR4.…”

mentioning

confidence: 94%

A Brucella spp. Protease Inhibitor Limits Antigen Lysosomal Proteolysis, Increases Cross-Presentation, and Enhances CD8+ T Cell Responses

Coria

Ibáñez

Tkach

et al. 2016

The Journal of Immunology

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In this study, we demonstrate that the unlipidated (U) outer membrane protein (Omp) 19 from Brucella spp. is a competitive inhibitor of human cathepsin L. U-Omp19 inhibits lysosome cathepsins and APC-derived microsome activity in vitro and partially inhibits lysosomal cathepsin L activity within live APCs. Codelivery of U-Omp19 with the Ag can reduce intracellular Ag digestion and increases Ag half-life in dendritic cells (DCs). U-Omp19 retains the Ag in Lamp-2+ compartments after its internalization and promotes a sustained expression of MHC class I/peptide complexes in the cell surface of DCs. Consequently, U-Omp19 enhances Ag cross-presentation by DCs to CD8+ T cells. U-Omp19 s.c. delivery induces the recruitment of CD11c+CD8α+ DCs and monocytes to lymph nodes whereas it partially limits in vivo Ag proteolysis inside DCs. Accordingly, this protein is able to induce CD8+ T cell responses in vivo against codelivered Ag. Antitumor responses were elicited after U-Omp19 coadministration, increasing survival of mice in a murine melanoma challenge model. Collectively, these results indicate that a cysteine protease inhibitor from bacterial origin could be a suitable component of vaccine formulations against tumors.

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“…In an effort to create an effective and safe vaccine against B. abortus, several research groups have developed subunit (recombinant proteins) [4][5][6][7][8][9][10][11][12], a DNA [13][14][15][16][17][18], or live vector vaccines (based on bacteria and viruses) [19][20][21][22]. All of these vaccines were safe when tested in animal models (laboratory mice), and some when tested in cattle.…”

Section: Introductionmentioning

confidence: 99%

Safety of the novel vector vaccine against Brucella abortus based on recombinant influenza viruses expressing Brucella L7/L12 and OMP16 proteins, in cattle

Tabynov¹,

Kydyrbayev²,

Ryskeldinova³

et al. 2014

J Vaccines Immunol

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Citation: Tabynov K, Kydyrbayev Z, Ryskeldinova S, Yespembetov B, Syrymkyzy N, et al. (2015) eertechz AbstractThis paper presents the results of a study of the safety of new vector vaccine against B. abortus based on recombinant influenza A subtype H5N1 or H1N1 (viral constructs vaccine formulation) viruses expressing Brucella ribosomal protein L7/L12 and Omp16, in cattle. To increase the effectiveness of the vaccine, adjuvants such as Montanide Gel01 or chitosan were included in its composition. Immunization of cattle (5 animals per group) with the viral constructs vaccine formulation only, or its combination with adjuvants Montanide Gel01 or chitosan, were conducted via the conjunctival method using cross prime (influenza virus subtype H5N1) and booster (influenza virus subtype H1N1) vaccination schedules. Vaccine candidates were evaluated in comparison with the positive (B. abortus S19) and negative (PBS) controls. Comprehensive studies involving thermometry and clinical examination, hematology and biochemical blood analysis, showed that all of the viral constructs vaccine formulation, as well as their combination with adjuvants, compared to the commercial bacterial vaccine B. abortus S19 were completely safe in cattle. Furthermore it is shown that the developed vaccines can effectively differentiate vaccinated animals from infected animals. Brucella L7/L12 or Omp16 proteins. The influenza A virus contains a segmented genome consisting of eight negative-strand RNA fragments. Of these, the smallest fragment (NS) -encoding two proteins: viral nonstructural protein (NS1) and nuclear export protein (Nep) -is a convenient target for genetic manipulation as NS1 is able to tolerate foreign sequences exceeding its own length [25]. Thus, the ORF of NS1 was used for inserting Brucella sequences in this study. The А/Puerto Rico/8/34 (H1N1) strain was used as the backbone for obtaining influenza A virus vectors expressing Brucella L7/L12 or Omp16 sequences in the form of fusion proteins with the N-terminal 124 amino acid residues of NS1.Our previous studies have shown that a bivalent vaccine formulation comprising a mixture of recombinant influenza A virus subtype H5N1 or H1N1 expressing the ribosomal L7/L12 or Omp16 proteins in prime and booster immunization mode (via conjunctival injection) in cattle induced a strong antigen-specific T-cell immune response, and most importantly provided a high level of protectiveness comparable to the commercial B. abortus S19 vaccine and superior to the B. abortus S19 vaccine in combination with Montanide Gel01 adjuvant [24]. Based on this, the next stage of our study was to evaluate the safety of the proposed new live vector vaccine in cattle. Additionally, we evaluated the possibility of differentiating infected animals from vaccinated animals using the developed vaccine.

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Immunization with Recombinant Brucella Species Outer Membrane Protein Omp16 or Omp19 in Adjuvant Induces Specific CD4 ⁺ and CD8 ⁺ T Cells as Well as Systemic and Oral Protection against Brucella abortus Infection

Cited by 24 publications

References 0 publications

Humoral Immunity and CD4+ Th1 Cells Are Both Necessary for a Fully Protective Immune Response upon Secondary Infection with Brucella melitensis

Humoral Immunity and CD4+ Th1 Cells Are Both Necessary for a Fully Protective Immune Response upon Secondary Infection with Brucella melitensis

A Brucella spp. Protease Inhibitor Limits Antigen Lysosomal Proteolysis, Increases Cross-Presentation, and Enhances CD8+ T Cell Responses

Safety of the novel vector vaccine against Brucella abortus based on recombinant influenza viruses expressing Brucella L7/L12 and OMP16 proteins, in cattle

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Immunization with Recombinant Brucella Species Outer Membrane Protein Omp16 or Omp19 in Adjuvant Induces Specific CD4 + and CD8 + T Cells as Well as Systemic and Oral Protection against Brucella abortus Infection

Cited by 24 publications

References 0 publications

Humoral Immunity and CD4+ Th1 Cells Are Both Necessary for a Fully Protective Immune Response upon Secondary Infection with Brucella melitensis

Humoral Immunity and CD4+ Th1 Cells Are Both Necessary for a Fully Protective Immune Response upon Secondary Infection with Brucella melitensis

A Brucella spp. Protease Inhibitor Limits Antigen Lysosomal Proteolysis, Increases Cross-Presentation, and Enhances CD8+ T Cell Responses

Safety of the novel vector vaccine against Brucella abortus based on recombinant influenza viruses expressing Brucella L7/L12 and OMP16 proteins, in cattle

Contact Info

Product

Resources

About

Immunization with Recombinant Brucella Species Outer Membrane Protein Omp16 or Omp19 in Adjuvant Induces Specific CD4 ⁺ and CD8 ⁺ T Cells as Well as Systemic and Oral Protection against Brucella abortus Infection