Use of a purified Trypanosoma cruzi antigen and CpG oligodeoxynucleotides for immunoprotection against a lethal challenge with trypomastigotes

Frank, Fernanda M.; Petray, Patricia; Cazorla, Silvia I.; Muñoz, M. Carmen; Corral, Ricardo S.; Malchiodi, Emilio L.

doi:10.1016/s0264-410x(03)00541-3

Cited by 57 publications

(45 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the subsequent experiments, we added a second adjuvant, CpG ODN 1826, to alum. We selected this adjuvant based on previous studies showing that CpG ODN 1826 could improve Th1 immune response and protective immunity to a T. cruzi infection induced by a purified native protein (6). At this point, the precise relevance of CpG ODN 1826 in our system is not clear.…”

Section: Discussionmentioning

confidence: 99%

CD8⁺-T-Cell-Dependent Control ofTrypanosoma cruziInfection in a Highly Susceptible Mouse Strain after Immunization with Recombinant Proteins Based on Amastigote Surface Protein 2

et al. 2005

View full text Add to dashboard Cite

We previously described that DNA vaccination with the gene encoding amastigote surface protein 2 (ASP-2) protects approximately 65% of highly susceptible A/Sn mice against the lethal Trypanosoma cruzi infection. Here, we explored the possibility that bacterial recombinant proteins of ASP-2 could be used to improve the efficacy of vaccinations. Initially, we compared the protective efficacy of vaccination regimens using either a plasmid DNA, a recombinant protein, or both sequentially (DNA priming and protein boosting). Survival after the challenge was not statistically different among the three mouse groups and ranged from 53.5 to 75%. The fact that immunization with a recombinant protein alone induced protective immunity revealed the possibility that this strategy could be pursued for vaccination. We investigated this possibility by using six different recombinant proteins representing distinct portions of ASP-2. The vaccination of mice with glutathione S-transferase fusion proteins representing amino acids 261 to 500 or 261 to 380 of ASP-2 in the presence of the adjuvants alum and CpG oligodeoxynucleotide 1826 provided remarkable immunity, consistently protecting 100% of the A/Sn mice. Immunity was completely reversed by the in vivo depletion of CD8 ؉ T cells, but not CD4 ؉ T cells, and was associated with the presence of CD8 ؉ T cells specific for an epitope located between amino acids 320 and 327 of ASP-2. We concluded that a relatively simple formulation consisting of a recombinant protein with a selected portion of ASP-2, alum, and CpG oligodeoxynucleotide 1826 might be used to cross-prime strong CD8؉ -T-cell-dependent protective immunity against T. cruzi infection.

show abstract

Section: Discussionmentioning

confidence: 99%

CD8⁺-T-Cell-Dependent Control ofTrypanosoma cruziInfection in a Highly Susceptible Mouse Strain after Immunization with Recombinant Proteins Based on Amastigote Surface Protein 2

et al. 2005

View full text Add to dashboard Cite

show abstract

“…On the other hand, the same antigen administered with CpG oligonucleotides induces a Th1 type immune response with elevated IFNγ production, which protects mice against infection by reducing parasitemia and increasing survival. 42 More recent studies are based on the use of recombinant proteins, which have now been extensively evaluated. Some of the most promising antigens tested include cruzipain, GP82, and several proteins from the transsialidase superfamily such as ASP-2 and TS, and all can provide significant protection in a variety of mouse models when administered with CpG oligonucleotides as adjuvants ( Table 1).…”

Section: Current Status Of Vaccine Researchmentioning

confidence: 99%

Advances and challenges towards a vaccine against Chagas disease

Quijano-Hernández

Dumonteil

2011

Human Vaccines

View full text Add to dashboard Cite

“…cruzi contains a major cysteine proteinase called cruzipain (Cz), which is displayed on the surface of the parasite and also accumulates in the lysosomes located near the flagellar pocket, from where it is secreted (46). Cz exhibits a number of attractive properties as a candidate antigen for vaccine development: (i) it is highly immunogenic in natural infection (34); (ii) it is present in the three main developmental stages of the parasite (i.e., epimastigote, amastigote, and trypomastigote) in all tested strains (40); (iii) it is a secreted antigen and its ability to cleave immunoglobulins has been proposed as an immunoescape mechanism (5); (iv) it plays an important role in the process of parasite internalization within mammalian cells (46); and (v) it is able to induce a protective immune response when coadministered with synthetic oligodeoxynucleotides carrying immunostimulatory CpG motifs (CpG-ODN) (17).…”

mentioning

confidence: 99%

“…Previous studies have documented the usefulness of Cz-based vaccines in eliciting protective immunity to T. cruzi (17,44,45). On the other hand, Salmonella is an ideal delivery system because is easy to handle and to manipulate genetically.…”

mentioning

confidence: 99%

“…As an additional strategy, prime-boost protocols were established in which mice primed with SCz were subsequently boosted with recombinant Cz (rCz) coadministered with different adjuvants. Two potent adjuvants were exploited, namely, (i) CpG-ODN motifs that enhance Th1 immune responses (11,27,42) by stimulating Toll-like receptor 9 (TLR-9) (24), previously reported as an efficacious adjuvant for native Cz to confer protection against T. cruzi after parenteral vaccination (17), and (ii) MALP-2, a synthetic derivative of a macrophage-activating lipopeptide of 2 kDa from Mycoplasma fermentans which acts as TLR-2/6 agonist after mucosal administration (6,7,41). Our results demonstrated that Salmonella-mediated delivery of Cz-DNA, alone or in combination with a boost with rCz and CpG-ODN or MALP-2, promotes the elicitation of an immune response able to control T. cruzi infection and the collateral damage to muscle tissues.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Oral Vaccination withSalmonella entericaas a Cruzipain-DNA Delivery System Confers Protective Immunity againstTrypanosoma cruzi

et al. 2008

Self Cite

View full text Add to dashboard Cite

To stimulate both local and systemic immune responses against Trypanosoma cruzi, Salmonella enterica serovar Typhimurium aroA was exploited as a DNA delivery system for cruzipain (SCz). In a murine model we compared SCz alone (GI) or coadministered with Salmonella carrying a plasmid encoding granulocyte-macrophage colony-stimulating factor (GII), as well as protocols in which SCz priming was followed by boosting with recombinant cruzipain (rCz) admixed with either CpG-ODN (GIII) or MALP-2, a synthetic derivative of a macrophage-activating lipopeptide of 2 kDa from Mycoplasma fermentans (GIV). The results showed that protocols that included four oral doses of SCz (GI) elicited mainly a mucosal response characterized by immunoglobulin A (IgA) secretion and proliferation of gut-associated lymphoid tissue cells, with weak systemic responses. In contrast, the protocol that included a boost with rCz plus CpG (GIII) triggered stronger systemic responses in terms of Cz-specific serum IgG titers, splenocyte proliferation, gamma interferon (IFN-␥) secretion, and delayed-type hypersensitivity response. Trypomastigote challenge of vaccinated mice resulted in significantly lower levels of parasitemia compared to controls. Protection was abolished by depletion of either CD4 ؉ or CD8 ؉ T cells. Parasite control was also evident from the reduction of tissue damage, as revealed by histopathologic studies and serum levels of enzymes that are markers of muscle injury in chronic Chagas' disease (i.e., creatine kinase, aspartate aminotransferase, and lactate dehydrogenase). Enhanced release of IFN-␥ and interleukin-2 was observed in GI and GII upon restimulation of splenocytes in the nonparasitic phase of infection. Our results indicate that Salmonella-mediated delivery of Cz-DNA by itself promotes the elicitation of an immune response that controls T. cruzi infection, thereby reducing parasite loads and subsequent damage to muscle tissues.

show abstract

Use of a purified Trypanosoma cruzi antigen and CpG oligodeoxynucleotides for immunoprotection against a lethal challenge with trypomastigotes

Cited by 57 publications

References 57 publications

CD8⁺-T-Cell-Dependent Control ofTrypanosoma cruziInfection in a Highly Susceptible Mouse Strain after Immunization with Recombinant Proteins Based on Amastigote Surface Protein 2

CD8⁺-T-Cell-Dependent Control ofTrypanosoma cruziInfection in a Highly Susceptible Mouse Strain after Immunization with Recombinant Proteins Based on Amastigote Surface Protein 2

Advances and challenges towards a vaccine against Chagas disease

Oral Vaccination withSalmonella entericaas a Cruzipain-DNA Delivery System Confers Protective Immunity againstTrypanosoma cruzi

Contact Info

Product

Resources

About

Use of a purified Trypanosoma cruzi antigen and CpG oligodeoxynucleotides for immunoprotection against a lethal challenge with trypomastigotes

Cited by 57 publications

References 57 publications

CD8+-T-Cell-Dependent Control ofTrypanosoma cruziInfection in a Highly Susceptible Mouse Strain after Immunization with Recombinant Proteins Based on Amastigote Surface Protein 2

CD8+-T-Cell-Dependent Control ofTrypanosoma cruziInfection in a Highly Susceptible Mouse Strain after Immunization with Recombinant Proteins Based on Amastigote Surface Protein 2

Advances and challenges towards a vaccine against Chagas disease

Oral Vaccination withSalmonella entericaas a Cruzipain-DNA Delivery System Confers Protective Immunity againstTrypanosoma cruzi

Contact Info

Product

Resources

About

CD8⁺-T-Cell-Dependent Control ofTrypanosoma cruziInfection in a Highly Susceptible Mouse Strain after Immunization with Recombinant Proteins Based on Amastigote Surface Protein 2

CD8⁺-T-Cell-Dependent Control ofTrypanosoma cruziInfection in a Highly Susceptible Mouse Strain after Immunization with Recombinant Proteins Based on Amastigote Surface Protein 2