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

Centro Interdisciplinar de Terapia Gênica, Universidade Federal de São Paulo, Escola Paulista de Medicina, São Paulo, SP, Brasil .
Memórias do Instituto Oswaldo Cruz (Impact Factor: 1.59). 07/2009; 104 Suppl 1:281-7. DOI: 10.1590/S0074-02762009000900037
Source: PubMed


Vaccines have had an unquestionable impact on public health during the last century. The most likely reason for the success of vaccines is the robust protective properties of specific antibodies. However, antibodies exert a strong selective pressure and many microorganisms, such as the obligatory intracellular parasite Trypanosoma cruzi, have been selected to survive in their presence. Although the host develops a strong immune response to T. cruzi, they do not clear the infection and instead progress to the chronic phase of the disease. Parasite persistence during the chronic phase of infection is now considered the main factor contributing to the chronic symptoms of the disease. Based on this finding, containment of parasite growth and survival may be one method to avoid the immunopathology of the chronic phase. In this context, vaccinologists have looked over the past 20 years for other immune effector mechanisms that could eliminate these antibody-resistant pathogens. We and others have tested the hypothesis that non-antibody-mediated cellular immune responses (CD4+ Th1 and CD8+ Tc1 cells) to specific parasite antigens/genes expressed by T. cruzi could indeed be used for the purpose of vaccination. This hypothesis was confirmed in different mouse models, indicating a possible path for vaccine development.

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    • "The second group of genes belonged to the family of cysteine-proteases (cruzipain) expressed in all of the different forms of the parasite. Other antigens formed a heterogeneous group including molecules such as the flagellar calcium-binding protein, paraflagellar rod protein-2, LYT-1 antigen, ribosomal protein L7a-like protein, and KMP11, among others (reviewed by [62, 63]). "
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    ABSTRACT: In the past ten years, studies have shown the recognition of Trypanosoma cruzi-associated molecular patterns by members of the Toll-like receptor (TLR) family and demonstrated the crucial participation of different TLRs during the experimental infection with this parasite. In the present review, we will focus on the role of TLR-activated pathways in the modulation of both innate and acquired immune responses to T. cruzi infection, as well as discuss the state of the art of vaccine research and development against the causative agent of Chagas disease (or American trypanosomiasis).
    Full-text · Article · Feb 2012 · Journal of Parasitology Research
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    • "It is well documented that type 1 immune responses are critical for protection against both mucosal and systemic T. cruzi infection (Hoft et al. 2000; Hoft & Eickhoff 2005; Rodrigues et al. 2009). CpG motifs presented within ssDNA are known to induce type 1 immune responses mediated by toll-like receptor 9 (TLR9) stimulation, and have been used safely and effectively in mice and humans (Cooper et al. 2005; Dumais et al. 2002; Krieg 2000). "
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    ABSTRACT: The potential use of the Trypanosoma cruzi metacyclic trypomastigote (MT) stage-specific molecule glycoprotein-82 (gp82) as a vaccine target has not been fully explored. We show that the opsonization of T. cruzi MT with gp82-specific antibody prior to mucosal challenge significantly reduces parasite infectivity. In addition, we investigated the immune responses as well as the systemic and mucosal protective immunity induced by intranasal CpG-adjuvanted gp82 vaccination. Spleen cells from mice immunized with CpG-gp82 proliferated and secreted IFN-γ in a dose-dependent manner in response to in vitro stimulation with gp82 and parasite lysate. More importantly, these CpG-gp82-immunized mice were significantly protected from a biologically relevant oral parasite challenge.
    Full-text · Article · Aug 2010 · Memórias do Instituto Oswaldo Cruz
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    ABSTRACT: 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, com-mensalic 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 mi-tochondrial 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 vari-able 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 in-sect 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].
    Full-text · Article · Jan 2010
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