A DNA‐priming protein‐boosting regimen significantly improves type 1 immune response but not protective immunity to <i>Trypanosoma cruzi</i> infection in a highly susceptible mouse strain

Vasconcelos, José Ronnie; Boscardin, Sílvia Beatriz; Hiyane, Meire Ioshie; Kinoshita, Sheila S.; Fujimura, Adriana E.; Rodrigues, Maurício M.

doi:10.1046/j.0818-9641.2002.01136.x

Cited by 31 publications

(33 citation statements)

References 24 publications

(33 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Finally, we immunized mice with a combined protocol consisting of priming with plasmid DNA followed by booster injections with recombinant proteins. This protocol was based on our previous study showing that the heterologous prime-boost immunization induced high levels of cell-mediated immunity against a Trypanosoma cruzi antigen (33). In spite of the immune responses induced by a heterologous prime-boost immunization with these genes or antigens after an i.d.…”

Section: Discussionmentioning

confidence: 99%

Testing of FourLeishmaniaVaccine Candidates in a Mouse Model of Infection withLeishmania(Viannia)braziliensis, the Main Causative Agent of Cutaneous Leishmaniasis in the New World

Salay

Dorta

Santos

et al. 2007

Clin Vaccine Immunol

View full text Add to dashboard Cite

We evaluated whether four recombinant antigens previously used for vaccination against experimental infection with Leishmania (Leishmania) major could also induce protective immunity against a challenge with Leishmania ( The protozoan parasite Leishmania (Viannia) braziliensis commonly causes localized cutaneous leishmaniasis (CL); however, a chronic mucosal leishmaniasis (ML) may develop in some infected individuals, with severe and progressive manifestations (reviewed in reference 11). At present, this species accounts for more than 90% of the 28,712 annual cases of CL and ML recorded in Brazil in 2004 (7). Although chemotherapies for CL and ML do exist, there are several limitations: (i) drug treatment is rarely affordable by those who need them, (ii) drug treatment requires daily injections of the drug for weeks, (iii) drug treatment can be associated with side effects, and (iv) drug resistance is becoming an increasing problem (13, 24; reviewed in references 3 and 32). To make matters worse, control of CL and ML is problematic due to the sylvatic nature of both vectors and reservoirs, making insecticide spraying and the elimination of reservoirs particularly difficult (26). Due to these difficulties, in the long run, the development of an effective vaccine may help both the prevention and the treatment of CL and ML caused by L. (V.) braziliensis.Most studies conducted thus far in vaccination against CL used genes and/or antigens isolated and characterized from Leishmania (Leishmania) major or L. (L.) amazonensis (8, 31; reviewed in references 9 and 21). Among the leading candidates to the development of a vaccine against CL, there are homologues of the receptor for activated C kinase protein (LACK or p36), Leishmania elongation and initiation factor (LeIF), L. (L.) major stress inducible protein 1 (LmSTI1), and thiol-specific antioxidant (TSA) from L. (L.) major (5, 6, 10, 14, 15, 28, and 30).Based on these promising prospects, the present study was designed to test whether four recombinant antigens previously used for vaccination against experimental infection with L. (L.) major (LACK, LmSTI1, LeIF, and TSA) could also generate protective immunity against an intradermal (i.d.) challenge with L. (V.) braziliensis. We considered this question very important because, as mentioned above, this species is responsible for most cases of CL and ML in Brazil and in the New World.

show abstract

Section: Discussionmentioning

confidence: 99%

Testing of FourLeishmaniaVaccine Candidates in a Mouse Model of Infection withLeishmania(Viannia)braziliensis, the Main Causative Agent of Cutaneous Leishmaniasis in the New World

Salay

Dorta

Santos

et al. 2007

Clin Vaccine Immunol

View full text Add to dashboard Cite

show abstract

“…Immunization. A/Sn mice were immunized according to protocols described earlier (3,29). Each mouse received 3 doses of 100 g of plasmid DNA injected intramuscularly at 0, 3, and 5 weeks.…”

Section: Methodsmentioning

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

“…In contrast, vaccination with a plasmid containing the ORF encoding the catalytic domain of T. cruzi TS failed to promote a similar degree of protective immunity (43,44). The same plasmid has been shown in many instances to be highly protective in BALB/c mice challenged with parasites of the Y or Tulahuen strain of T. cruzi (11,22,27).…”

Section: Discussionmentioning

confidence: 97%

“…Most importantly, immunization with this plasmid promoted the survival of approximately 65% of the mice against a lethal T. cruzi infection (43). Protective immunity of this magnitude could not be duplicated by immunization with a plasmid encoding a trypomastigote-specific antigen (T. cruzi TS) (43,44). Based on the data obtained following infection in this mouse model, we considered that perhaps antigens expressed by the intracellular amastigote forms of T. cruzi would be better targets for protective immune responses.…”

mentioning

confidence: 99%

Novel Protective Antigens Expressed by Trypanosoma cruzi Amastigotes Provide Immunity to Mice Highly Susceptible to Chagas' Disease

Silveira

Claser

Haolla

et al. 2008

Clin Vaccine Immunol

View full text Add to dashboard Cite

Earlier studies have demonstrated in A/Sn mice highly susceptible to Chagas' disease protective immunity against lethal Trypanosoma cruzi infection elicited by vaccination with an open reading frame (ORF) expressed by amastigotes. In our experiments, we used this mouse model to search for other amastigote-expressed ORFs with a similar property. Fourteen ORFs previously determined to be expressed in this developmental stage were individually inserted into a eukaryotic expression vector containing a nucleotide sequence that encoded a mammalian secretory signal peptide. Immunization with 13 of the 14 ORFs induced specific antibodies which recognized the amastigotes. Three of those immune sera also reacted with trypomastigotes and epimastigotes. After a lethal challenge with Y strain trypomastigotes, the vast majority of plasmid-injected mice succumbed to infection. In some cases, a significant delay in mortality was observed. Only two of these ORFs provided protective immunity against the otherwise lethal infection caused by trypomastigotes of the Y or Colombia strain. These ORFs encode members of the trans-sialidase family of surface antigens related to the previously described protective antigen amastigote surface protein 2 (ASP-2). Nevertheless, at the level of antibody recognition, no cross-reactivity was observed between the ORFs and the previously described ASP-2 from the Y strain. In immunofluorescence analyses, we observed the presence of epitopes related to both proteins expressed by amastigotes of seven different strains. In conclusion, our approach allowed us to successfully identify two novel protective ORFs which we consider interesting for future studies on the immune response to Chagas' disease.

show abstract

A DNA‐priming protein‐boosting regimen significantly improves type 1 immune response but not protective immunity to Trypanosoma cruzi infection in a highly susceptible mouse strain

Cited by 31 publications

References 24 publications

Testing of FourLeishmaniaVaccine Candidates in a Mouse Model of Infection withLeishmania(Viannia)braziliensis, the Main Causative Agent of Cutaneous Leishmaniasis in the New World

Testing of FourLeishmaniaVaccine Candidates in a Mouse Model of Infection withLeishmania(Viannia)braziliensis, the Main Causative Agent of Cutaneous Leishmaniasis in the New World

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

Novel Protective Antigens Expressed by Trypanosoma cruzi Amastigotes Provide Immunity to Mice Highly Susceptible to Chagas' Disease

Contact Info

Product

Resources

About

A DNA‐priming protein‐boosting regimen significantly improves type 1 immune response but not protective immunity to Trypanosoma cruzi infection in a highly susceptible mouse strain

Cited by 31 publications

References 24 publications

Testing of FourLeishmaniaVaccine Candidates in a Mouse Model of Infection withLeishmania(Viannia)braziliensis, the Main Causative Agent of Cutaneous Leishmaniasis in the New World

Testing of FourLeishmaniaVaccine Candidates in a Mouse Model of Infection withLeishmania(Viannia)braziliensis, the Main Causative Agent of Cutaneous Leishmaniasis in the New World

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

Novel Protective Antigens Expressed by Trypanosoma cruzi Amastigotes Provide Immunity to Mice Highly Susceptible to Chagas' Disease

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