Swimming against the current: genetic vaccination against Trypanosoma cruzi infection in mice

Rodrigues, Maurício M.; Alencar, Bruna Cunha de; Claser, Carla; Tzelepis, Fanny; Silveira, Eduardo Lani Volpe da; Haolla, Filipe Augusto Bettencourt; Dominguez, Mariana Ribeiro; Vasconcelos, José Ronnie

doi:10.1590/s0074-02762009000900037

Cited by 17 publications

(13 citation statements)

References 61 publications

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“…In addition to a more balanced humoral response, mTS-IMX formulation improved the activation of primed CD4 + T Th1 and CD8 + T lymphocytes in terms of IFN-␥ production. Both CD4 + and CD8 + T subpopulations are known to play a pivotal role in controlling T. cruzi infection [44][45][46][47][48]. Accordingly, mTS-driven IFN-␥ production by CD4 + T cells might favor elimination of parasites by activated macrophages and help IgG2a antibody production, coinciding with our observations ( Fig.…”

Section: Discussionsupporting

confidence: 91%

Efficacy of a trans-sialidase-ISCOMATRIX subunit vaccine candidate to protect against experimental Chagas disease

Bontempi

Vicco

Cabrera

et al. 2015

Vaccine

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Section: Discussionsupporting

confidence: 91%

Efficacy of a trans-sialidase-ISCOMATRIX subunit vaccine candidate to protect against experimental Chagas disease

Bontempi

Vicco

Cabrera

et al. 2015

Vaccine

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“…Characterization of these antigens allowed studies with recombinant proteins based on isolated, antigenspecific genes. Different antigens alone and mixtures of distinct adjuvants, plasmid DNA and, more recently, recombinant viruses and bacteria have been tested as T. cruzi vac-cines [370]. Various antigens delivered using distinct delivery systems have been able to induce protective immune responses in a mouse model of T. cruzi infection as measured by a reduction in acute-phase parasitemia, tissue parasitism and mortality [370].…”

Section: Chagas Disease: Trypanosoma Cruzimentioning

confidence: 99%

Trypanosomatids: Odd Organisms, Devastating Diseases

Lopes¹,

Souto-Padrón²,

Dias³

et al. 2010

TOPARAJ

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Trypanosomatids cause many diseases in and on animals (including humans) and plants. Altogether, about 37 million people are infected with Trypanosoma brucei (African sleeping sickness), Trypanosoma cruzi (Chagas disease) and Leishmania species (distinct forms of leishmaniasis worldwide). The class Kinetoplastea is divided into the subclasses Prokinetoplastina (order Prokinetoplastida) and Metakinetoplastina (orders Eubodonida, Parabodonida, Neobodonida and Trypanosomatida) [1,2]. The Prokinetoplastida, Eubodonida, Parabodonida and Neobodonida can be free-living, commensalic or parasitic; however, all members of theTrypanosomatida are parasitic. Although they seem like typical protists under the microscope the kinetoplastids have some unique features. In this review we will give an overview of the family Trypanosomatidae, with particular emphasis on some of its "peculiarities" (a single ramified mitochondrion; unusual mitochondrial DNA, the kinetoplast; a complex form of mitochondrial RNA editing; transcription of all protein-encoding genes polycistronically; trans-splicing of all mRNA transcripts; the glycolytic pathway within glycosomes; T. brucei variable surface glycoproteins and T. cruzi ability to escape from the phagocytic vacuoles), as well as the major diseases caused by members of this family. However, the present review does not cover all trypanosomatids; for example, the insect trypanosomatids are underrepresented here. On the other hand, reviews on this particular group of parasites have been written by experts in the field [3-12].

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“…Vaccines that boost CD8 ϩ T cells recognizing TS-derived epitopes can enhance control of T. cruzi (21,38,53,54), but only to a limited degree, as TS-based immunizations fail to provide sterilizing protection from infection (55). Given this less-thanstellar protective capacity of current vaccines targeted for TS family molecules, identification of normally subdominant CD8 ϩ T cells that could be expanded by vaccination and that may provide better protection is of significant interest.…”

Section: How Critical For Control Of Infection Are Cd8mentioning

confidence: 99%

Long-Term Immunity to Trypanosoma cruzi in the Absence of Immunodominanttrans-Sialidase-Specific CD8⁺T Cells

et al. 2016

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c Trypanosoma cruzi infection drives the expansion of remarkably focused CD8؉ T cell responses targeting epitopes encoded by variant trans-sialidase (TS) genes. Infection of C57BL/6 mice with T. cruzi results in up to 40% of all CD8 ؉ T cells committed to recognition of the dominant TSKB20 and subdominant TSKB18 TS epitopes. However, despite this enormous response, these mice fail to clear T. cruzi infection and subsequently develop chronic disease. One possible reason for the failure to cure T. cruzi infection is that immunodomination by these TS-specific T cells may interfere with alternative CD8 ؉ T cell responses more capable of complete parasite elimination. To address this possibility, we created transgenic mice that are centrally tolerant to these immunodominant epitopes. Mice expressing TSKB20, TSKB18, or both epitopes controlled T. cruzi infection and developed effector CD8 ؉ T cells that maintained an activated phenotype. Memory CD8 ؉ T cells from drug-cured TSKB-transgenic mice rapidly responded to secondary T. cruzi infection. In the absence of the response to TSKB20 and TSKB18, immunodominance did not shift to other known subdominant epitopes despite the capacity of these mice to expand epitope-specific T cells specific for the model antigen ovalbumin expressed by engineered parasites. Thus, CD8؉ T cell responses tightly and robustly focused on a few epitopes within variant TS antigens appear to neither contribute to, nor detract from, the ability to control T. cruzi infection. These data also indicate that the relative position of an epitope within a CD8؉ immunodominance hierarchy does not predict its importance in pathogen control.

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Swimming against the current: genetic vaccination against Trypanosoma cruzi infection in mice

Cited by 17 publications

References 61 publications

Efficacy of a trans-sialidase-ISCOMATRIX subunit vaccine candidate to protect against experimental Chagas disease

Efficacy of a trans-sialidase-ISCOMATRIX subunit vaccine candidate to protect against experimental Chagas disease

Trypanosomatids: Odd Organisms, Devastating Diseases

Long-Term Immunity to Trypanosoma cruzi in the Absence of Immunodominanttrans-Sialidase-Specific CD8⁺T Cells

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Swimming against the current: genetic vaccination against Trypanosoma cruzi infection in mice

Cited by 17 publications

References 61 publications

Efficacy of a trans-sialidase-ISCOMATRIX subunit vaccine candidate to protect against experimental Chagas disease

Efficacy of a trans-sialidase-ISCOMATRIX subunit vaccine candidate to protect against experimental Chagas disease

Trypanosomatids: Odd Organisms, Devastating Diseases

Long-Term Immunity to Trypanosoma cruzi in the Absence of Immunodominanttrans-Sialidase-Specific CD8+T Cells

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Long-Term Immunity to Trypanosoma cruzi in the Absence of Immunodominanttrans-Sialidase-Specific CD8⁺T Cells