Trypanosoma cruzi
5693
Organ and tissue damage during acute T cruzi infection is caused by the parasite itself and by the host's acute immunoinflammatory response, which is elicited by the presence of the parasite. Findings from several studies in experimental models of T cruzi infection have suggested that a strong T-helper-1 immune response with both CD4 and CD8 cells, and characterised by the production of some specific cytokines—such as interferon γ, tumour necrosis factor α, and interleukin 12—is important in the control of parasitism. By comparison, production of interleukin 10 and transforming growth factor β is related to parasite replication by inhibition of macrophage trypanocidal activity. The T-helper-1 immune response has a protective role mainly through the synthesis of nitric oxide, which exerts a potent trypanocidal action. During chronic infection, the balance between immune-mediated parasite containment and damaging inflammation of the host tissues probably determines the course of disease. If the immunological response is inefficient, or paradoxically leads to tissue damage, both parasite load and immune-mediated inflammation increase. By contrast, a well executed immune response, in which parasite burden is lowered and inflammatory consequences are kept to a minimum, results in reduced tissue damage (Rassi et al., 2010).
Chagas disease
Chagas disease is transmitted to human beings and to more than 150 species of domestic animals (eg, dogs, cats, and guineapigs) and wild mammals (eg, rodents, marsupials, and armadillos) mainly by large, blood-sucking reduviid bugs of the subfamily Triatominae, within three overlapping cycles: domestic, peridomestic, and sylvatic. Although more than 130 species of triatomine bugs have been identified, only a handful are competent vectors for T cruzi. Triatoma infestans, Rhodnius prolixus, and Triatoma dimidiata are the three most important vector species in the transmission of T cruzi to man (Rassi et al., 2010).
Chagas disease is a chronic, systemic, parasitic infection caused by the protozoan Trypanosoma cruzi, and was discovered in 1909. The disease affects about 8 million people in Latin America, of whom 30-40% either have or will develop cardiomyopathy, digestive megasyndromes, or both. In the past three decades, the control and management of Chagas disease has undergone several improvements. Large-scale vector control programmes and screening of blood donors have reduced disease incidence and prevalence. Although more effective trypanocidal drugs are needed, treatment with benznidazole (or nifurtimox) is reasonably safe and effective, and is now recommended for a widened range of patients. Improved models for risk stratification are available, and certain guided treatments could halt or reverse disease progression (Rassi et al., 2010).
Baboon
Papio cynocephalus
9556
Bank vole
Clethrionomys glareolus
447135
Bear
Ursus americanus
9643
Birds
Passeroidea
175121
Brown Trout
Salmo trutta
8032
Buffalo
Bison bison
9901
Carnivores
Vulpes
9625
Cat
Felis catus
9685
Catfishes
Siluriformes
7995
Cattle
Bos taurus
9913
Chicken
Gallus gallus
9031
Chimpanzee
Pan troglodytes
9598
chinchillas
Chinchillidae
10150
Copper Pheasant
Syrmaticus soemmerringii
9067
Deer
Cervus elaphus
9860
Deer mouse
Peromyscus maniculatus
10042
Dog
Canis familiaris
9615
Ducks
Anas
8835
Ferret
Mustela putorius furo
9669
Fish
Hyperotreti
117565
Gerbil
Gerbillina
10045
Goat
Capra hircus
9925
Gray wolf
Canis lupus
9612
Guinea pig
Cavia porcellus
10141
Hamster
Mesocricetus auratus
10036
Horse
Equus caballus
9796
Human
Homo sapiens
9606
Macaque
Macaca fascicularis
9541
Mongolian Gerbil
Meriones unguiculatus
10047
Monkey
Platyrrhini
9479
Mouse
Mus musculus
10090
None
None
Parrot
Psittacidae
9224
Pig
Sus scrofa
9823
Rabbit
Oryctolagus cuniculus
9986
Rainbow trout
Oncorhynchus mykiss
8022
Rat
Rattus
10114
Raven
Corvus corax
56781
sei whale
Balaenoptera borealis
9768
Sheep
Ovis aries
9940
Squirrel
Spermophilus richardsonii
37591
Tree shrew
Tupaiidae
9393
Trouts, salmons & chars
Salmoninae
504568
Turkey
Meleagris gallopavo
9103
Vole
Microtus ochrogaster
79684
Water buffalo
Bubalus bubalis
391902
T. cruzi DNA prime/Protein-boost vaccine encoding TcG2 and TcG4
Prime-boost vaccine with DNA vaccine priming
Research
Intramuscular injection (i.m.)
A DNA-prime/protein boost therapeutic vaccine encoding TcG2 and TcG4 aimed to determine if GPx1, an antioxidant, protects the heart form chagasic pathogenesis. (Gupta et al., 2015)
IL-12 and GM-CSF (Gupta et al., 2015) - IL-12 and GM-CSF expression plasmids were used as adjuvants because these cytokines induce antigen presentation and B and T cell responses. (Gupta and Garg, 2013)
Intramuscular injection (i.m.)
TcG2 and TcG4 (Gupta et al., 2015) - T. cruzi encoding plasmids which have elicited a strong Th1 - type antibody response dominated by immunoglobin G2b (IgG2b)/IgG1 isotypes. (Bhatia and Garg, 2008)
DNA vaccine construction
DNA vaccine construction
Myocardial degeneration with enlarged myocytes was particularly evident in chagasic WT mice. Therapeutic vaccination resulted in a substantial decline in myocardial and skeletal muscle levels of inflammatory infiltrate in chagasic WT mice. (Gupta et al., 2015)
C57BL/6
Mice were infected with T. cruzi (10,000 trypomastigotes per mouse, intraperitoneal). Forty-five days later, mice were immunized with the 1st vaccine dose consisting of the TcG2- and TcG4-encoding plasmids with IL-12- and GM-CSF-expression plasmids (25-μg each plasmid DNA/mouse, intramuscularly). Twenty one days after the primary immunization, mice were given 2nd vaccine dose constituted of recombinant proteins (TcG2 and TcG4, 25 μg of each protein emulsified in 5 μg saponin/100 μl PBS/mouse, intradermally). (Gupta et al., 2015)
Chronically-infected GPxtg mice presented a lower level of inflammatory infiltrate in heart and skeletal muscle therefore the antioxidants aided in arresting the chronic infiltration of the inflmamatory infiltrate in the heart in chagasic mice. (Gupta et al., 2015)
GPxtg
T. cruzi DNA prime/rTc80 + ODN-CpG boost vaccine
Recombinant vector vaccine
Research
Intramuscular injection (i.m.)
T. cruzi vaccine involving priming with Tc80 DNA delivered by a bacterial vector followed by a boosting with rTc80 + ODN - CpG (Bivona et al., 2018)
CpG (Bivona et al., 2018)
Intramuscular injection (i.m.)
Tc80 (Bivona et al., 2018)
DNA vaccine construction
Mice immunized at least twice with the recombinant protein (Pboost group) elicited antibody titers considerably higher than control group. Pboost group showed an IgG2a/IgG1 ratio about 25-fold higher than rTc80im group, indicating that STc80 priming accentuated the bias towards a Th1 response. (Bivona et al., 2018)
C3H/HeN
Mice were immunized with four doses separated by ten days. Mice received two does of Tc80 DNA delivered by the attenuated Salmonella (1x10^9 CFU/mouse) followed by two does of 10 ug rTc80 + 10 ug CpG - ODN intramuscularly. Control group mice were intramuscularly injected twice with PBS + 10 ug CpG-ODN and then two does of attenuated Salmonella carrying an empty plasmid pcDNA 3.1 orally. (Bivona et al., 2018)
Immunized groups showed a decreased parasitemia and higher survival rate compared with non-immunized control mice. Moreover, during the chronic phase of the infection, immunized mice presented: lower levels of myopathy-linked enzymes, parasite burden, electrocardiographic disorders and inflammatory cells. (Bivona et al., 2018)
Two weeks after last immunization, immunized female C3H/HeN mice were challenged intraperitoneally with 200 blood trypomastigotes of T. cruzi strain RA. (Bivona et al., 2018)
T. cruzi DNA vaccine encoding ASP-2
VO_0004375
DNA vaccine
Research
pGEX-3X [Ref2271:Araújo et al., 2005]
Intramuscular injection (i.m.)
Intramuscular injection (i.m.)
DNA vaccine construction
Vector pGEX-3X expressed amastigote surface protein 2 (ASP-2 ) (Araújo et al., 2005).
Vaccination with a plasmid expressing amastigote surface protein 2 (ASP-2) generates specific CD4+ Th1 and CD8+ Tc1 immune responses (Araújo et al., 2005).
VO_0000286
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 (Araújo et al., 2005).
T. cruzi DNA Vaccine encoding CRP-10 Protein
DNA vaccine
Research
pBC12BI [Ref1354:Sepulveda et al., 2000]
Intramuscular injection (i.m.)
Intramuscular injection (i.m.)
DNA vaccine construction
BALB/c and C3H/HeJ
100 μg of pBC12BI.crp-daf DNA or vector DNA was dissolved in 50 μl of PBS and injected intramuscularly in the tibialis anterior muscles of mice that had been briefly anesthetized by metaphane inhalation (Sepulveda et al., 2000).
Mice immunized with the crp DNA plasmid produced antibodies capable of lysing the parasites in the presence of complement and were protected against a lethal challenge with T. cruzi trypomastigotes (Sepulveda et al., 2000).
BALB/c mice immunized with DNA were challenged intravenously (i.v.) 2 weeks after the last boost with 2 × 10^6 T. cruzi strain Y trypomastigotes (Sepulveda et al., 2000).
T. cruzi DNA Vaccine encoding G2 Protein
DNA vaccine
Research
pCDNA3
Intramuscular injection (i.m.)
Intramuscular injection (i.m.)
DNA vaccine construction
C57BL/6
C57BL/6 mice were injected in the quadriceps muscle thrice at 2-week intervals with antigen-encoding plasmid (pCDNA3.TcG2 25 μg per DNA/mouse) and cytokine-encoding plasmids (pcDNA3.msp35, pcDNA3.msp40 [IL-12], and pCMVI.GM-CSF; 25 μg per plasmid DNA/mouse) (Bhatia and Garg, 2008).
The dominant IgG2b/IgG1 antibody response was maintained after a challenge infection and was associated with 50% control of the acute-phase tissue parasite burden and an almost undetectable level of tissue parasites during the chronic phase (Bhatia and Garg, 2008).
Two weeks after the last immunization, mice were challenged with culture-derived T. cruzi trypomastigotes (2.5 × 10^4/mouse, intraperitoneally) and sacrificed at days 30, 75, and 120 postinfection (p.i.), corresponding to the acute phase of peak parasitemia, the intermediate phase of immune control of parasites, and the chronic phase of disease development, respectively (Bhatia and Garg, 2008).
T. cruzi DNA Vaccine encoding G4 Protein
DNA vaccine
Research
pCDNA3
Intramuscular injection (i.m.)
Intramuscular injection (i.m.)
DNA vaccine construction
C57BL/6 mice were injected in the quadriceps muscle thrice at 2-week intervals with antigen-encoding plasmid (pCDNA3.TcG4 25 μg per DNA/mouse) and cytokine-encoding plasmids (pcDNA3.msp35, pcDNA3.msp40 [IL-12], and pCMVI.GM-CSF; 25 μg per plasmid DNA/mouse) (Bhatia and Garg, 2008).
The dominant IgG2b/IgG1 antibody response was maintained after a challenge infection and was associated with 50% control of the acute-phase tissue parasite burden and an almost undetectable level of tissue parasites during the chronic phase (Bhatia and Garg, 2008).
Two weeks after the last immunization, mice were challenged with culture-derived T. cruzi trypomastigotes (2.5 × 10^4/mouse, intraperitoneally) and sacrificed at days 30, 75, and 120 postinfection (p.i.), corresponding to the acute phase of peak parasitemia, the intermediate phase of immune control of parasites, and the chronic phase of disease development, respectively (Bhatia and Garg, 2008).
T. cruzi DNA vaccine encoding PFR Ag + IL-12
DNA vaccine
Research
Intramuscular injection (i.m.)
T. cruzi DNA vaccine encoding PFR Ag coadsorbed to alum with either recombinant IL-12 or adenovirus-expressing IL-12. (Wrightsman and Manning, 2000)
Freund's complete adjuvant and Freund's incomplete adjuvant
Intramuscular injection (i.m.)
PFR Ag (Wrightsman and Manning, 2000)
T cells and CD4+ T cells from mice immunized with either PFR Ag/Freund's or PFR Ag/alum/IL12 secreted high levels of IFN-γ in the presence of macrophages incubated with PFR Ag or macrophages infected with T. cruzi. Only negligible amounts of IFN-γ were observed with the CD8+ T cell population, and no measurable IFN-γ could be detected when any of these T cells were incubated with untreated macrophages. (Wrightsman and Manning, 2000)
Six- to 8-week-old female C57BL/6J mice were immunized by subcutaneous (s.c.) injection with 40 μg PFR protein adsorbed to alum or emulsified with Freund's complete adjuvant. The mice were boosted twice at two-week intervals with 20 μg PFR protein adsorbed to alum or emulsified with Freund's incomplete adjuvant. Alum-PFR Ag mixtures were prepared by combining equal volumes of Rehsorpter aluminum hydroxide adsorptive gel and PFR Ag at 400 μg/ml in 0.9% saline with gentle mixing for 1 h at room temperature. In some experiments murine recombinant IL-12 (rIL-12; a generous gift from Genetics Institute, Cambridge, MA) was mixed with the PFR protein during the adsorption procedure. The amount of rIL-12 added to the mixture gave a final concentration of either 0.5 μg rIL-12/40 μg PFR (initial immunization) or 0.5 μg rIL-12/20 μg PFR (boosts). (Wrightsman and Manning, 2000)
Two weeks after the last injection, mice were challenged with s.c. injection of 102 bloodstream trypomastigotes. Following challenge, mice were checked daily, and survival was recorded at days postinfection. (Wrightsman and Manning, 2000)
T. cruzi DNA vaccine encoding PFR2 fused with HSP70
pCMV4-PFR2-H70
Recombinant vector vaccine
Research
Intramuscular injection (i.m.)
T. cruzi DNA vector vaccine containing the PFR2 and PFR3 genes fused to HSP70
CpG (Morell et al., 2006)
Intramuscular injection (i.m.)
PFR2 and PFR3 genes (Morell et al., 2006) - paraflagellar rod proteins present in the flagellum of T. cruzi that induce an immune respons that results in reduction in the level of circulating parasites.
Recombinant protein preparation
High antibody titers were present 2 weeks after the third dose in the sera of the BALB/c mice immunized with the constructs containing the PFR2 gene alone or fused to HSP70 gene. The mice immunized with the plasmid bearing only the PFR3 gene or fused to the HSP70 gene also reached significant anti-PFR3 reactivity after the fourth immunization. The percentage of spleen cells expressing IFN-γ and IL12 was significantly higher (p < 0.05) in mice immunized with the PFR2-HSP70 fused genes than that observed in mice that received saline solution, empty pCMV4 vector or the PFR2 coding gene alone. In the mice immunized with the PFR2-HSP70 fused genes a lower percentage of cells expressing IL4 was also observed relative to that observed in mice that received saline solution, empty pCMV4 vector or the PFR2 coding gene alone. In contrast, an increase in the number of cells expressing IL-4 was observed in mice immunized with the PFR3-HSP70 fused genes, although it was not statistically significant. (Morell et al., 2006)
BALB/c + C57BL/6
Groups of nine BALB/c and of five C57BL/6-A2.1/Kb mice were intramuscularly injected with 100 μg of plasmids: pCMV4 (control), pCMV4-PFR2, and pCMV4-PFR3 (carrying PFR2 and PFR3 gene, respectively) and pCMV4-PFR2-H70 and pCMV4-PFR3-H70 (bearing the PFR2-HSP70 and PFR3-HSP70 fused genes, respectively) in 100 μl. Sterile 0.9% sodium chloride solution was injected to the control group. Each mouse was immunized four times at 3-week intervals. Groups of five immunized BALB/c and B6-A2/Kb mice were used to determine the induced cellular response. (Morell et al., 2006)
Two out of eight control mice that received saline solution died at days 26 and 27 post-infection. One mouse of the group of eight mice inoculated with pCMV4 died at day 30 post-infection. In contrast, in mice immunized with the PFR2 gene or the PFR2-HSP70 construct circulating parasites could be detected only the first 3 weeks post-infection. Parasites could not be detected afterwards. Mice immunized with the PFR3 gene or the PFR3-HSP70 construct were able to control infection at week fourth post-infection. Controls mice controlled infection at week fifth post-infection. (Morell et al., 2006)
Groups of four immunized BALB/c mice were challenged with 2.5 × 103 of attenuated trypomastigote forms 10 weeks after the last immunization. The protection assays were carried in two of the three experiments done to analyze the immune response. (Morell et al., 2006)
T. cruzi DNA vaccine encoding TcSSP4
DNA vaccine
Research
Intramuscular injection (i.m.)
T. cruzi DNA vaccine encoding TcSSP4 protein emulsified in Freund's complete adjuvant aimed to induce an immune response (Arce-Fonseca et al., 2011)
Freund's Complete Adjuvant (Arce-Fonseca et al., 2011)
Intramuscular injection (i.m.)
TcSSP4 (Arce-Fonseca et al., 2011)
When compared with controls, statistically significant differences were found in IL-6 levels in mice immunized with either rTcSSP4 protein or pBCSSP4 plasmid. The IL-6 levels were higher at 3h (p<0.01) and lower at 12 h (p<0.01). For TNF-α, statistically significant differences were found in mice immunized with rTcSSP4 protein at 3 h (p<0.01) and 12 h (p<0.01) when compared with control mice, and no significant differences were found in mice immunized with pBCSSP4 plasmid. However, a clear difference was found regarding IFN-γ production; only 3 h sera from animals immunized with the pBCSSP4 plasmid showed significant amounts of this cytokine. No detectable amounts of IFN-γ were found in the other conditions. (Arce-Fonseca et al., 2011)
BALB/c
For protein immunization, each mouse was immunized i.p. with 10 μg of rTcSSP4 protein emulsified with Freund's complete adjuvant. DNA immunizations were done twice at 2 week intervals in the tibialis anterioris muscle with the plasmids pBCSSP4 or pBk-CMV resuspended in PBS. (Arce-Fonseca et al., 2011)
Mice immunized with the rTcSSP4 protein were challenged i.p. with 1x10^4 or 3x10^4 bloodstream trypomastigotes (BT) 3 or 7 days post-immunization. Mice immunized with DNA were challenged 2 weeks after the last immunization with 1x104 BT. Parasitemia was monitored every 3 days. (Arce-Fonseca et al., 2011)
T. cruzi DNA vaccine encoding TcTASV-C
DNA vaccine
Research
Intramuscular injection (i.m.)
T. cruzi DNA vaccine encoding the TcTASV-C protein adminstrated with U-Omp19
U-Omp19 (Caeiro et al., 2020) - protein that has protease inhibitor activity and can partially inhibit lysosomal cysteine proteases that limit degradation of the co-administered antigen inside antigen presenting cells. (Coria et al., 2016)
Intramuscular injection (i.m.)
TcTASV-C (Caeiro et al., 2020) - highly conserved antigen in different strains of T. cruzi and is mainly found in extracellular vesicles and has a great expression increment in bloodstream trypomastigotes in vivo. These features indicate that TcTASV-C may play a role during the early acute phase of infection. (Caeiro et al., 2018)
Mice immunized with TcTASV-C and formulations with aluminum hydroxide induced a specific IgG immune response with titers higher than 6400. The TcTASV-C + U-Omp19 vaccinated group showed an IgG response similar to the group immunized with the protein alone (titer: 3200). Mixed IgG1 and IgG2a responses were observed with all the different adjuvants formulations tested. However, in the TcTASV-C + PBS group the specific response was mostly IgG1. The TcTASV-C + U-Omp19 immunization scheme induced IFN-γ and IL-17 production in a dose-dependent manner regarding the TcTASV-C concentration used for cell stimulation. This did not occur with TcTASV-C + PBS immunization or with TcTASV-C and all adjuvants together. (Caeiro et al., 2020)
C3H/He
C3H/He mice (n = 5 per group) were vaccinated with recombinant proteins. Briefly, three doses of subcutaneous injections of mixed TcTASV-CGST and TcTASV-CHIS (25 µg each one) with a colloidal suspension of aluminum hydroxide (Sigma), 25 µg of saponin (Sigma) and/or purified 150 µg of U-Omp19-His [60], [22]. Control groups were immunized with the same procedure but with 50 μg of GST or with TcTASV-C with PBS as adjuvant. (Caeiro et al., 2020)
After T. cruzi challenge, the IgG2a response was predominant, with antibodies of IgG1 isotype in surviving mice at 90 d.p.i. resulting undetectable.
Fifteen days after the last dose, mice were challenged with 100 bloodstream trypomastigotes of the RA strain by the intraperitoneal route. (Caeiro et al., 2020)
T. cruzi DNA vaccine encoding trans-sialidase
DNA vaccine
Research
Intramuscular injection (i.m.)
T. cruzi DNA vaccine encoding the trans-sialidase gene intended to fight T. cruzi infection and induce an immune response (Rodrigues et al., 1999)
Intramuscular injection (i.m.)
trans-sialidase - In past studies, immunization of BALB/c mice with the TS gene elicited immune responses, as measured by antibody production and T-cell activation and had a significant reduction in peak parasitemia and survived lethal T. cruzi infection (Costa et al., 1998)
T. cruzi DNA vaccine encoding TSA-1 and Tc24
VO_0004532
DNA vaccine
Research
pcDNA3.1 [Ref2650:Quijano-Hernández et al., 2013]
Intramuscular injection (i.m.)
Intramuscular injection (i.m.)
DNA vaccine construction
DNA vaccine construction
Both preventive and therapeutic vaccination significantly reduced parasitemia, cardiac inflammation and cardiac parasite burden, and tended to reduce the development of cardiac arrhythmias (Quijano-Hernández et al., 2013).
T. cruzi DNA Vaccine encoding TSA-1 protein
DNA vaccine
Research
VR1012 (Vical Inc., San Diego, Calif.)
Intramuscular injection (i.m.)
Intramuscular injection (i.m.)
DNA vaccine construction
B6 and BALB/c
Groups of B6 and BALB/c mice were injected intramuscularly into each tibialis anterior muscle with 50 μg of VR1012 TSA1.7, VR1012 TSA2.1, or control VR1012 suspended in 50 μl of PBS by using a 27-gauge needle. Mice were boosted 4 weeks later with an identical dose of plasmid (100 μg total) given by the same bilateral intramuscular injection (Wizel et al., 1998).
When TSA-1 DNA-vaccinated animals were challenged with T. cruzi, 14 of 22 (64%) H-2(b) and 16 of 18 (89%) H-2(d) mice survived the infection (Wizel et al., 1998).
Two weeks after the second dose, animals were infected by intraperitoneal injection of 10^5 (B6) or 10^3 (BALB/c) T. cruzi BFT. Parasitemias were monitored periodically by hemacytometer counts of 10 μl of tail vein blood in an ammonium chloride solution (Wizel et al., 1998).
T. cruzi DNA vaccine encoding TSA-1, ASP-1, ASP-2
VO_0004374
DNA vaccine
Research
pCMVI.UBF3/2 [Ref2270:Garg and Tarleton, 2002]
Intramuscular injection (i.m.)
IL-12, GM-CSF (Garg and Tarleton, 2002)
Intramuscular injection (i.m.)
DNA vaccine construction
Vector pCMVI.UBF3/2 expressed TSA-1 (Garg and Tarleton, 2002).
DNA vaccine construction
Vector pCMVI.UBF3/2 expressed ASP-2 cDNA (Garg and Tarleton, 2002).
DNA vaccine construction
Vector pCMVI.UBF3/2 expressed ASP-1 cDNA (Garg and Tarleton, 2002).
Immunization of mice with plasmids encoding ASP-1, ASP-2, or TSA-1 elicited poor antigen-specific cytotoxic-T-lymphocyte (CTL) activity and T. cruzi-specific antibody responses. Codelivery of interleukin-12 and granulocyte-macrophage colony-stimulating factor plasmids with antigen-encoding plasmids resulted in a substantial increase in CTL activity and antibody production and in increased resistance to T. cruzi infection (Garg and Tarleton, 2002).
VO_0000286
Immunization with this mixture of ts-encoding plasmids elicited moderate parasite-specific antibody responses and substantial CTL activity and subsequently provided significant resistance to T. cruzi infection. In conclusion, genetic vaccines composed of ASP-1, ASP-2, and TSA-1 provide partial protection from lethal T. cruzi infection (Garg and Tarleton, 2002).
T. cruzi DNA vaccine encoding TSSA
DNA vaccine
Research
Intramuscular injection (i.m.)
T. cruzi DNA vaccine encoding TSSA antigen enhanced by IL-12 adjuvant
IL - 12 (Katae et al., 2002) - adjuvant that expands the CD8+ T cell population to control an infection and plays a significant role in the modulation of the CTL response (Gherardi et al., 2001)
Intramuscular injection (i.m.)
TSSA (Katae et al., 2002)
T. cruzi DNA Vaccine pGFP-TSA1
VO_0001390
DNA vaccine
Research
pGFP plasmid (Clontech, Palo Alto, CA)
Gene Gun
Gene Gun
DNA vaccine construction
C57BL/6
B6 mice were immunized four times at two-week intervals with 6 μg of each plasmid using a Helios Gene Gun (BioRad, NY, USA) (Chou et al., 2008).
C57BL/6 mice vaccinated with this plasmid showed suppressed parasitemia and prolonged survival. Vaccination with pGFP-TSA1 enhanced epitope-specific cytotoxicity and IFN-gamma secretion by CD8(+)T cells (Chou et al., 2008).
Two weeks after the last vaccination, mice were infected with 1000 blood-derived T. cruzi trypomastigotes by s.c. injection at the base of the tail. Parasitemia levels were evaluated by counting the number of parasites in 5 μl of blood from the tail vein (Chou et al., 2008).
T. cruzi DNA vaccine pTS encoding T. cruzi antigens
VO_0004377
DNA vaccine
Research
pcDNA3.1 [Ref2273:Eickhoff et al., 2011]
Intramuscular injection (i.m.)
IL-15 (Eickhoff et al., 2011)
Intramuscular injection (i.m.)
DNA vaccine construction
Vector pcDNA3 expressed T. cruzi antigens, including trans-sialidase (TS) (Eickhoff et al., 2011).
Vaccination of mice with pTS alone or pTS + pIL-15 elicited strong TS-specific T cell responses as detected 3 months after vaccination. In addition to enhancing TS-specific CD8+ T cell responses, the pIL-15 adjuvant enhanced TS-specific CD4+ T cell responses induced by pTS vaccination (Eickhoff et al., 2011).
VO_0000286
We challenged 5 mice per group with a lethal dose of T. cruzi BFT (5,000 BFT s.c.) 30 days following the final immunization, and followed survival for >2 months. All mice vaccinated with pTS (with or without pIL-15 co-immunization) survived lethal T. cruzi challenge, whereas all mice vaccinated with pIL-15 alone died (Eickhoff et al., 2011).
T. cruzi DNA vaccine pUB-ASP-2
VO_0004376
DNA vaccine
Research
pcDNA3.1 [Ref2272:Chou et al., 2010]
Intramuscular injection (i.m.)
Intramuscular injection (i.m.)
DNA vaccine construction
Vector pcDNA3.1 expressed amastigote surface protein 2 (ASP-2 ) (Chou et al., 2010).
The absolute number of both IFN-γ+CD8+ T cells and GZM-b+CD8+ T cells in the spleen was significantly higher in pUB-ASP-2 immunized mice. Immunization with pUB-ASP-2 promotes CD8+ T cell activation, and enhances the expression level of IFN-γ and GZM-b in CD8+ T cells (Chou et al., 2010).
VO_0000286
After being challenged with T. cruzi, mice immunized with pUB-ASP-2 developed a lower parasitemia than control pcDNA immunized groups; survival was also prolonged by immunization with pUB-ASP-2. Six out of seven pUB-ASP-2 immunized mice survived until the end of the experiment (Chou et al., 2010).
T. cruzi DNA-prime/MVA-boost vaccine encoding TcG2 and TcG4
Prime-boost vaccine with DNA vaccine priming
Research
Two vectors: pCDA3.1 plasmid DNA vaccine vector, and the MVA vaccine vector
Intramuscular injection (i.m.)
The vaccine uses a DNA-prime/MVA-boost regimen, which includes two components: (1) a DNA vaccine with pCDNA3.1 encoding T. cruzi TcG2 and TcG4, and (2) a recombinant Modified Vaccinia Ankara (MVA) viral vector expressiong the same T. cruzi TcG2 and TcG4. The DNA vaccine is used for priming vaccination, and t he MVA recombinant vaccine is used for booster vaccination (Gupta and Garg, 2012).
Intramuscular injection (i.m.)
TcG2 and TcG4 (Gupta and Garg, 2012) - antigens phylogenetically conserved in clinically important T. cruzi strains, expressed in infective and intracellular stages of the parasite, and recognized by parasite-specific cellular and humoral immune responses in multiple T. cruzi-infected hosts (Bhatia et al., 2004).
DNA vaccine construction
DNA vaccine construction
Mice immunized with TcG2 and TcG4 elicited a strong parasite and antigen-specific type 1 (IgG2b>IgG1) antibody response. indicating that delivery of antigens by DNA/rMVA approach primed the immunized mice to respond with pathogen-specific effector antibodies. Indeed, challenge infection resulted in a rapid and potent expansion of antibody response in immunized mice. (Gupta and Garg, 2012)
C57BL/6
C57BL/6 mice were injected with pCDNA3.TcG2 or pCDNA3.TcG4 (25-μg/mouse, i.m.), and corresponding rMVA (106-pfu/mouse, i.d.) at 3-weeks interval (controls: empty vector). (Gupta and Garg, 2012)
Two-weeks after the last immunization, mice were challenged with T. cruzi (10,000 trypomastigotes/mouse, i.p.). (Gupta and Garg, 2012)
T. cruzi PAR1 Protein Vaccine
VO_0001391
Subunit vaccine
Research
Subcutaneous Injection
Alum
Subcutaneous Injection
Recombinant protein preparation
C57BL/6
Six-to-eight-week-old female C57BL/6 mice were immunized by subcutaneous (s.c.) injection of 40 μg of pPFR or rPFR proteins co-adsorbed to alum with 0.5 μg recombinant murine IL-12 and were boosted twice at 2-week intervals with 20 μg protein co-adsorbed to alum with 0.5 μg rIL-12 (Luhrs et al., 2003).
rPFR-1 immunized animals were able to successfully resolve parasitemia by day 30 p.i., with the peak parasitemia occurring between days 17 and 21 p.i. (Luhrs et al., 2003).
Two weeks after the last injection, mice were challenged with s.c. injection of 10^2 bloodstream Peru strain trypomastigotes (Luhrs et al., 2003).
T. cruzi PAR2 Protein Vaccine
VO_0001392
Subunit vaccine
Research
Subcutaneous Injection
Alum
Subcutaneous Injection
Recombinant protein preparation
C57BL/6
Six-to-eight-week-old female C57BL/6 mice were immunized by subcutaneous (s.c.) injection of 40 μg of pPFR or rPFR proteins co-adsorbed to alum with 0.5 μg recombinant murine IL-12 and were boosted twice at 2-week intervals with 20 μg protein co-adsorbed to alum with 0.5 μg rIL-12 (Luhrs et al., 2003).
rPFR-2 immunized animals were able to successfully resolve parasitemia by day 30 p.i., with the peak parasitemia occurring between days 17 and 21 p.i. (Luhrs et al., 2003).
Two weeks after the last injection, mice were challenged with s.c. injection of 10^2 bloodstream Peru strain trypomastigotes (Luhrs et al., 2003).
T. cruzi Tc24 vaccine
Subunit vaccine
Research
Intramuscular injection (i.m.)
Vaccine containing recombinant protein Tc24 formulated with an emulsion containing the Toll-like receptor 4 against E6020 to combat chronic T. cruzi infection. (Barry et al., 2019)
Toll-like receptor 4 agonist E6020 (Barry et al., 2019)
Intramuscular injection (i.m.)
Tc24 (Barry et al., 2019) - Tc24 has been found to induce strong CD8+ T-cell responses in past studies and has shown promise to be effective against a wide diversity of T. cruzi parasite strains (Arnal et al., 2020)
Recombinant protein preparation
The vaccine elicits a greater than 5-fold increase in Tc24-specific secreted IFNγ compared to the Tc24 control. IgG2a, a mouse antibody isotype associated with a TH1-bias, is most robust in the vaccine compared to the controls, further validating the cytokine results. In comparison, both the Tc24+E6020-SE vaccine and the Tc24 control produce a robust IgG1 antibody response. These results indicate that the Tc24 recombinant protein is capable of producing an antigen-specific immune response, but that the E6020-SE adjuvant is necessary to induce a favorable TH1-biasing of the resulting immune response. (Barry et al., 2019)
BALB/c
Mice were infected with T. cruzi and allowed to progress past the acute phase of disease, characterized by elevated parasitemia resolving by 40 days post-infection, before vaccination at 70 days post-infection with Tc24+E6020-SE or a sham vaccine. (Barry et al., 2019)
T. cruzi Tsf-ISPA vaccine
Subunit vaccine
Licensed
subcutaneous injection
A T. cruzi subunit trans-sialidase (TSf - ISPA) based vaccine which aims to target MDSCs (myeloid derived suppressor cells)
ISPA - immunostimulent-particle adjuvant (Gamba et al., 2021)
subcutaneous injection
TsF (trans-sialidase) - In previous studies, a trans-sialidase based vaccine was able to confer protection against a virulent T.cruzi strain, stimulating the effector immune response and decreasing C11b+ GR-1 splenocytes significantly.
Recombinant protein preparation
PBS-treated mice do not tolerate a challenge with 900 Tulahuen T. cruzi parasites if MDSCs are depleted by 5FU treatment at day 15 p.i. In contrast, a proportion of TSf-ISPA-immunized and infected mice tolerated and survived infection allowing the in vivo study of the influence of MDSCs on several components of the effector and regulatory immune response during the acute phase of T. cruzi infection. TSf-ISPA immunization causes a slight but significant increase of CD11b+ GR-1+ splenocytes, here we also targeted those cells at the stage of immunization, prior to T. cruzi challenge. Notably, 5FU administration before each dose of TSf-ISPA vaccine was able to significantly ameliorate survival and decrease parasitemia levels of TSf-ISPA-vaccinated and infected mice.(Gamba et al., 2021)
BALB/c
BALB/ mice were immunized with three subcutaneous doses, one every two weeks, containing 10ug of a fraction of the trans-sialidase protein (TSf) with 3 ul of ISPA as adjuvant. Control groups were immunized with phosphate buffered saline (PBS) solution, following the same protocol.(Gamba et al., 2021)
Mice were challenged intraperitoneally with 900 or 1500 bloodstream trypomastigotes of Tulahuen strain, as indicated, 15 days after the last immunization.(Gamba et al., 2021)
T. cruzi Vaccine encoding ASP2 with Rapamycin
DNA vaccine
Research
Intramuscular injection (i.m.)
This prime-booster vaccine encoding ASP2 alongside rapamycin treatment is made by having pCDNA plasmid encoding ASP2 and a recombinant replication-deficient human adenovirus type 5 (HuAd5) vaccine vector also encoding ASP2 (Rigato et al., 2011),; futhermore, the rapamycin treatment is used as an adjuvant to enhance the vaccine immune response (Moraschi et al., 2021).
Rapamycin - the pharmalogical inhibitor of mTOR (Moraschi et al., 2021)
Intramuscular injection (i.m.)
ASP2 (Moraschi et al., 2021)
DNA vaccine construction
The ASP2 antigen is expressed in the
The number of CD8+ T-cells that simultaneously express IFNγ, TNF and CD107a, named polyfunctional subpopulation, were increased in rapamycin-treated mice (Gr.3), compared with vehicle-injected mice (Gr.2). the magnitude of responding CD8+ T-cells (frequency of cells that express at least one of the three molecules IFNγ or TNF or CD107a after ex vivo stimulus with the specific peptide) was also higher in rapamycin treated mice (Moraschi et al., 2021).
C57BL/6
The protocol consists of a dose of plasmid DNA, with the vectors pcDNA3 (control) or pIgSPClone9, at 10 or 100 μg/mouse. Three weeks after the first immunization, mice were immunized with 2 x 10^7 or 2 x 10^8 pfu of the adenoviral vectors Adβ-Gal (control) or AdASP-2. Both immunizations were performed by intramuscular route in the Tibialis anterior muscle. Experimental groups were delineated as follows: 1) Control: immunized with the control vectors pcDNA3 and Adβ-Gal; 2) ASP2: immunized with pIgSPCl.9/AdASP-2 and vehicle-injected (PBS); 3) ASP2/rapamycin: immunized with pIgSPCl.9/AdASP-2 and rapamycin-treated. Mice were treated every 24 hours with 2 μg rapamycin (Sigma Aldrich) per mouse (0.075 mg/kg/day), diluted in 0.2 mL PBS via intraperitoneal (i.p.) for 34 days, starting at priming. Control mice were treated with the vehicle (PBS) (Moraschi et al., 2021).
T. cruzi vaccine encoding pBKTcENO
DNA vaccine
Research
Intramuscular injection (i.m.)
A recombinant vaccine encoding pKBTcENO emulsified in PBS (Arce-Fonseca et al., 2018)
Intramuscular injection (i.m.)
pBKTcENO (Arce-Fonseca et al., 2018)
The immunizations with pBKTcENO induced a significant production of IgGs against the rTcENO antigen seven days after the last immunization. The mice immunized with pBKTcENO showed IgG2a>IgG2b>IgG1 with an IgG2b/IgG1 ratio > 1, suggesting that a predominantly Th1-like immune response was induced. The pBKTcENO plasmid reduced the parasite load in the mice at 70% and 42% during the parasitemia peak (day 24 after challenge) compared to the PBS and pBK-CMV controls, respectively. All mice immunized with pBKTcENO eventually died, not exceeding day 33 post-infection. (Arce-Fonseca et al., 2018)
BALB/c
All mice (female BALB/c mice 6–8 weeks old) were randomly assigned into control or vaccinated groups of eight mice each. 100 μg of recombinant plasmid (pBKTcENO) or vector DNA (pBK-CMV) (Stratagene) was dissolved in 50 μL of sterile PBS, injected intramuscularly (i.m.) in the tibialis anterioris muscle and boosted twice every 2 weeks. Two weeks after the last immunization, they received an i.p. injection of 8 × 104 bloodstream trypomastigotes of T. cruzi. (Arce-Fonseca et al., 2018)
T. cruzi vaccine encoding recombinant enolase from H8 strain
Recombinant vector vaccine
Research
Intraperitoneal injection (i.p.)
Vaccine encoding rTcENO (recombinant enloase) from the H8 strain emulsified in Freund's Complete Adjuvant and Freund's Incomplete Adjuvant (Arce-Fonseca et al., 2018)
Freund's complete Adjuvant and Freund's incomplete adjuvant (Arce-Fonseca et al., 2018)
Intraperitoneal injection (i.p.)
Recombinant enolase from T. cruzi H8 strain (Arce-Fonseca et al., 2018)
The immunizations with rTcENO induced a significant production of IgGs against the rTcENO antigen seven days after the last immunization. Antigen-specific isotypes of immunoglobulins in the sera of immunized animals with rTcENO revealed high levels of IgG1>IgG2b>IgG2a, indicating that this antigen induced a mixed Th1-/Th2-like immune response. The mice immunized with rTcENO exhibited high titers of antibodies compared to the control groups inoculated with PBS or pBK-CMV. (Arce-Fonseca et al., 2018)
BALB/c
All mice were randomly assigned into control or vaccinated groups of eight mice each in two independent experiments. The mice were immunized by intraperitoneal (i.p.) injection with 10 μg of the recombinant protein (rTcENO) emulsified in Freund's complete adjuvant (CFA) (Sigma) and boosted twice with 10 μg of the rTcENO in Freund's incomplete adjuvant (IFA) every 2 weeks. were randomly assigned into control or vaccinated groups of eight mice each in two independent experiments. The mice were immunized by intraperitoneal (i.p.) injection with 10 μg of the recombinant protein (rTcENO) emulsified in Freund's complete adjuvant (CFA) (Sigma) and boosted twice with 10 μg of the rTcENO in Freund's incomplete adjuvant (IFA) every 2 weeks. (Arce-Fonseca et al., 2018)
Challenged the immunized mice with a lethal dose of T. cruzi. The mice immunized with rTcENO showed typical immunoglobulins for Th1/Th2 immune responses, a significant reduction in the level of parasite burden in the blood, and 75% survival rate in comparison to the control groups. Moreover, the detection of IFN-γ, TNF (alpha and beta), and IL-2, but not IL-4, showed a polarized Th1 immune response when mice were challenged with T. cruzi. (Arce-Fonseca et al., 2018)
T. cruzi vaccine encoding Tc80
DNA vaccine
Research
Intramuscular injection (i.m.)
T. cruzi sub-unit vaccine formulated with recombinant Tc80 plus oligodeoxynucleotides CpG (ODN-CpG) as adjuvant. (Bivona et al., 2018)
CpG (Bivona et al., 2018)
Intramuscular injection (i.m.)
Tc80 (Bivona et al., 2018)
DNA vaccine construction
Mice elicited antibody titers considerably higher than control group. Splenocyts from all immunized mice were able to secrete IL-2 and IFN-y upon antigen recall. Mice presented a higher percentage of IFN-y and TNF-a producing CD4+ T cells compared with control group. (Bivona et al., 2018)
C3H/HeN
Mice were immunized with four doses separated by ten days intramuscularly in the quadriceps with 10ug of rTc80 adjuvanted with 10 ug of ODN-CpG 1826. Control group mice were intramuscularly injected twice with PBS + 10 ug CpG-ODN and then two does of attenuated Salmonella carrying an empty plasmid pcDNA 3.1 orally. (Bivona et al., 2018)
All immunized mice presented significantly reduced parasitemias during the acute phase of infection compared to the control. rTc80im group achieved the highest control of parasitemia. (Bivona et al., 2018)
Two weeks after the last dose of vaccination protocols, immunized male C3H/HeN mice were challenged intraperitoneally with 2.5x105 blood trypomastigotes of the sub-lethal T. cruzi strain K98. (Bivona et al., 2018)
T. cruzi vaccine encoding TcG2 and TcG4
DNA vaccine
Research
Intramuscular injection (i.m.)
A DNA vaccine containing recombinant proteins TcG2 and TcG4 formulated with fTr (fixed T. rangeli) epimastigotes (Gupta et al., 2019).
fTr and Quil A (Gupta et al., 2019)
fTr - fixed T. rangeli epimastigotes appeared to lower the blood parasitemia and tissue parasite foci in dogs (Aparicio-Burgos et al., 2015).
Quil A - in past studies, immunization of mice with a small concentration of antigens prepared with Quil A, a saponin derivative, induced strong antibody and cell-mediated immune responses (Araujo and Morein, 1991).
Intramuscular injection (i.m.)
TcG2 and TcG4 (Gupta et al., 2019) - antigens phylogenetically conserved in clinically important T. cruzi strains, expressed in infective and intracellular stages of the parasite, and recognized by parasite-specific cellular and humoral immune responses in multiple T. cruzi-infected hosts (Bhatia et al., 2004).
DNA vaccine construction
DNA vaccine construction
TcG2/TcG4 vaccine adjuvanted with fTr also resulted in maximal levels of Tc-specific IgG sub-types. Tr-specific IgGs constituted of IgG1, IgG2a, and IgG2b subtypes were also detected in mice that received fTr as an adjuvant with TcG2/TcG4 DNA or as a booster vaccine, and maximal Tr-specific antibodies were measured in sera of mice given fTr as an adjuvant with TcG2/TcG4. (Gupta et al., 2019)
C57BL/6
Mice were vaccinated in following groups: DNA vaccine only, two doses; DNA vaccine + fTr, two doses; DNA vaccine + QA, two doses; DNA vaccine + fTr + QA, two doses. To determine if fTr boosts the DNA vaccine-induced immune responses, mice were vaccinated with DNA vaccine followed by fTr (gp5) or fTr+QA (gp6). Each dose of DNA vaccine was constituted of 25-μg of each plasmid (pCDNA3.TcG2 and pCDNA3.TcG4) and delivered in 100 μl PBS by intramuscular (im) injection in the hind thighs. When used, fTr (1 × 108 Tr in 100 μl PBS) was delivered by subcutaneous (sc) injection. When added, vaccine was emulsified with 5 μg QA per dose per mouse. Non-vaccinated (N) mice were used as controls. Prime and booster doses of vaccine were given at 21-day intervals. (Gupta et al., 2019)
Mice were immunized, challenged with Tc (10,000 trypomastigotes/mouse, intraperitoneal) at 21 days after the 2nd vaccine dose, and euthanized at 21 days' post-infection (pi). Non-vaccinated mice infected with Tc (T) and euthanized at similar time-points were used as controls. (Gupta et al., 2019)
T. cruzi Vaccine TcVac2
DNA vaccine
Research
Intramuscular injection (i.m.)
TcVAc2 is a DNA-prime/protein-boost subunit vaccine (TcVac2) constituted of candidate antigens (TcG1-, TcG2-, and TcG4) along with adjuvants IL-12 and GM-CSF.(Gupta and Garg, 2010)
IL-12 and GM-CSF - IL-12 and GM-CSF expression plasmids were used as adjuvants because these cytokines induce antigen presentation and B and T cell responses (Gupta and Garg, 2013)
Intramuscular injection (i.m.)
TcG1, TcG2, and TcG4 (Gupta and Garg, 2010) - T. cruzi encoding plasmids which have elicited a strong Th1 - type antibody response dominated by immunoglobin G2b (IgG2b)/IgG1 isotypes. (Bhatia and Garg, 2008)
DNA vaccine construction
DNA vaccine construction
We detected a substantial level of TcTL- and TcG1-, TcG2- and TcG4-specific IgG antibodies in mice immunized with TcVac2. The level of antigen-specific antibody response was detected in the order of TcG4>TcG2>TcG1; and the antigen-specific antibody response was predominantly of the Th1 type with IgG2b/IgG1 ratio>1. (Gupta and Garg, 2010)
C57BL/6
C57BL/6 mice were injected in the quadriceps muscle twice at three-week intervals with antigen-encoding plasmids and cytokine-encoding plasmids. Mice were then immunized with two doses of TcG1-, TcG2-, and TcG4- recombinant proteins (25 µg each, total 75 µg protein emulsified in 5 µg saponin/100 µl PBS/mouse, intra-dermal). (Gupta and Garg, 2010)
Two weeks after the last immunization, mice were challenged with T. cruzi (10,000 trypomastigotes/mouse, i.p.).(Gupta and Garg, 2010)
T. cruzi Vaccine TcVac3 encoding TcG2 and TcG4
DNA vaccine
Research
plasmid vector [Ref5667:Gupta and Garg, 2013]
Intramuscular injection (i.m.)
DNA-prime/MVA-boost vaccine (TcVac3) constituted of antigenic candidates (TcG2 and TcG4) (Gupta and Garg, 2013)
IL-12 and GM-CSF - IL-12 and GM-CSF expression plasmids were used as adjuvants because these cytokines induce antigen presentation and B and T cell responses (Gupta and Garg, 2013).
Intramuscular injection (i.m.)
TcG2 and TcG4 (Gupta and Garg, 2013) - T. cruzi encoding plasmids which have elicited a strong Th1 - type antibody response dominated by immunoglobin G2b (IgG2b)/IgG1 isotypes. (Bhatia and Garg, 2008)
DNA vaccine construction
DNA vaccine construction
C57BL/6
Mice were injected with antigen-encoding plasmids with our without IL-12 and GM-CSF encoding plasmids. Three weeks later, mice were given booster vaccine constituted of rMVA.TcG2 and rMVA.TcG4. Mice injected with empty vectors were used as controls. (Gupta and Garg, 2013)
Two weeks after the last immunization, mice were challenged with T. cruzi. Mice were sacrificed at day 30 and 120-post infection corresponding to the acute phase of peak parasitemia and the chronic phase of disease development, respectively. (Gupta and Garg, 2013)
T. cruzi Vaccine TcVac4
Prime-boost vaccine with DNA vaccine priming
Research
Intramuscular injection (i.m.)
A DNA - prime/T. rangeli - boost (TcVac4) vaccine encoding TcG1, TcG2, and TcG4 antigens plus IL-12 and GM-CSF-encoding plasmids(Aparicio-Burgos et al., 2015)
IL - 12 and GM - CSF (Aparicio-Burgos et al., 2015) - IL-12 and GM-CSF expression plasmids were used as adjuvants because these cytokines induce antigen presentation and B and T cell responses (Gupta and Garg, 2013)
Intramuscular injection (i.m.)
TcG1, TcG2, and TcG4 (Aparicio-Burgos et al., 2015) - T, cruzi encoding plasmids which have elicited a strong Th1 - type antibody response dominated by immunoglobin G2b (IgG2b)/IgG1 isotypes. (Bhatia and Garg, 2008)
DNA vaccine construction
DNA vaccine construction
DNA vaccine construction
Immunization with TcVac4, delivered as two doses of subunit DNA vaccine and two doses of TrIE, elicited a strong parasite-specific IgG response with predominance of IgG2 subtype (IgG2/IgG1 = 2.7). Upon challenge infection, IgG1 response was expanded and IgG2 response barely changed, resulting in a balanced IgG2/IgG1 ratio (0.95) in TcVac4/Tc dogs. (Aparicio-Burgos et al., 2015)
Mongrel
Randomly assigned dogs to the following groups: a) pcDNA3.1/ no Tc(empty plasmid DNA and no challenge infection, n = 6); b) pcDNA3.1/Tc (empty plasmid followed by Tc challenge infection, n = 6); c) TcVac4/Tc (two doses of DNA vaccine followed by two doses of TrIE and challenge infection, n = 6); and d) TrIE/Tc (two doses of TrIE followed by challenge infection, n = 3). Each dose of DNA vaccine was delivered at two sites; intramuscular (180 μg each DNA in 0.9 ml PBS) and intradermal (20 μg each DNA in 0.1 ml PBS). TrIE vaccine was also delivered at two sites; subcutaneous (0.9x109 TrIE in 0.9 ml PBS-saponin) and intradermal (1x108 TrIE in 0.1 ml PBS- saponin).(Aparicio-Burgos et al., 2015)
Challenge infection with T. cruzi (3.5 x 10^3 culture-derived trypomastigotes/kg body weight, intraperitoneally) was performed six weeks after the last vaccine dose. The selected dose of the parasites was sufficient to produce acute parasitemia within 1–2 weeks of inoculation, and electrocardiographic changes within 6–8 weeks post-infection. All dogs were observed daily for general physical condition, at weekly intervals for clinical condition, and at 2-week intervals for cardiac function.(Aparicio-Burgos et al., 2015)
T. cruzi vaccine using attenuated Salmonella expressing T. cruzi Cruzipain
VO_0001393
Recombinant vector vaccine
Research
χ4550 attenuated Salmonella enterica serovar Typhimurium strain
Intranasally
IL-12
Intranasally
Recombinant vector construction
BALB/c
Mice were vaccinated four times intranasally with control and cruzipain-expressing salmonella cells. The mice were lightly anesthetized with ketamine-xylazine given intraperitoneally, and salmonella vaccines were administered in 10-μl volumes of PBS. A total of 2 × 10^6 CFU of salmonella was given for primary vaccinations, and 2 × 10^7 CFU of salmonella was given for booster vaccinations. The second vaccinations were given 4 weeks after the priming doses, and the three booster vaccinations were given at 2-week intervals (Schnapp et al., 2002).
As early as 15 days after immunization, the parasitemias detected in the cruzipain-immunized group were significantly lower than those in the phage10-immunized and unimmunized groups. Significantly reduced parasitemias persisted in the cruzipain-immunized group throughout the remainder of the first month postchallenge (Schnapp et al., 2002).
One month after the final vaccinations, the mice were challenged orally with 2,000 T. cruzi IMT (Schnapp et al., 2002).
T. cruzi vaccine using Sendai virus vector expressing amastigote surface protein-2
VO_0001394
Recombinant vector vaccine
Research
recombinant Sendai virus vector rSeV/dF
Intranasally
Intranasally
Parasite antigen amastigote surface protein-2 (ASP2) (Duan et al., 2009).
Recombinant vector construction
C57BL/6
B6 mice were administrated intranasally with 5 × 10^6 CIU SeV-GFP or SeV-ASP2 (Duan et al., 2009).
C57BL/6 mice immunized intranasally with rSeV/dF expressing ASP2 showed significantly suppressed parasitemia and could be protected from lethal T. cruzi challenge (Duan et al., 2009).
For challenge infections, mice were inoculated with 1000 blood-derived trypomastigotes at the base of the tail 2 weeks after immunization (Duan et al., 2009).
T. cruzi vector vaccine encoding Tc80
Recombinant vector vaccine
Research
attenuated Salmonella [Ref5711:Bivona et al., 2018]
Intramuscular injection (i.m.)
A T. cruzi attenuated bacterial Salmonella vector vaccine delivering the Tc80 gene.
Intramuscular injection (i.m.)
Tc80 (Bivona et al., 2018)
Recombinant vector construction
The gene is embedded and expressed by the T. cruzi attenuated bacterial Salmonella vector vaccine.
STc80 group which was immunized only with Tc80 DNA carried by Salmonella, did not elicit significant specific antibody titer comparing to SaroA. Antibodies isotypes reflected a Th1-biased response since IgG2a levels were higher than IgG1. Splenocytes from all immunized mice were able to secrete IL-2 and IFN -y upon antigen recall. STc80 group presented a significantly higher percentage of IFN-y or TNF-a producing CD4+ T cells. (Bivona et al., 2018)
C3H/HeN
Mice received 4 doses of attenuated Salmonella carrying a Tc80-coding eukaryotic plasmid separated by ten days via oral administration (1x10^9 CFU/mouse). Control group mice were intramuscularly injected twice with PBS + 10 ug CpG-ODN and then two does of attenuated Salmonella carrying an empty plasmid pcDNA 3.1 orally. (Bivona et al., 2018)
All immunized mice presented significantly reduced parasitemias during the acute phase of infection compared to the control. (Bivona et al., 2018)
Two weeks after last immunization, immunized female C3H/HeN mice were challenged intraperitoneally with 200 blood trypomastigotes of T. cruzi strain RA. (Bivona et al., 2018)
amastigote surface protein-2
VO_0011289
3537357
284180153
CDD:240366
CDD:271234
5693
?
amastigote surface protein-2
6.84
70196.77
785
ASP-2
>ADB82626.1 amastigote surface protein-2, partial [Trypanosoma cruzi]
MLSRVAAVKAPRTHNRHRVTGSSGRRREGRESEPQRPDMSWRAFTSAVLLLLLVIICCGSGAADAVEGKS
GAVQLPKWVDIFVPEKTHVLPKEGSESGVKKAFAAPSLVSAGGVMVAFAEGLFGHNVHGYDLFGIRPYEI
LAGYIKAAESWPSIVAEVNASTWRAHTVIGSRNGNDRLCFLYRPTAVARENKVFLLVGSDTVGYDSDDDM
WVKDGWDIQLVEGVATQSTDGKPSKTINWGEPKSLLKQVPKHTQDQLRDVVTAGGSGIVMQNNTFVFPLV
VNGKNYPFSSITYSTDNGNNWVFPESISPVGCLDPRITEWETGQILMIVDCGNGQSVYESRDMGKTWTEA
IGTLSGVWVKSRSGFRWDEGLRVDALITATIEGRKVMLYTQRGCASGEKEANALYLWVTDNNRTFHVGPV
AMDSAVNETLSNALLYSDGNLHLLKQRANEKGSALSLARLTEELKEIDSVLSTWARLDASFSASSTPTAG
LVGFLSNTSSGGDTWNDEYRCVDASVTKASKVKNGIKFTGPGSMATWLVNSREDNRQYGFVNHSFTLVAT
VTIHQVAKGSTPLLGAGLDAPVSTNFIGLSYSMDKRWETVFYGKKTTSNTTWELGKEYQVALMLQDGNKG
SVYVDGVIVGSPENITKLGALGHEIAHFYFGGDEGYINSSVTVTNVFLYNRPLSVGELKMVRKSDDKKGN
GGD
Protective antigen
To examine the efficacy of a new mode of recombinant viral vaccine, a vaccine was constructed of two non-transmissible Sendai viruses (rSeV/dF) encoding the full-length parasite antigen amastigote surface protein-2 (ASP2) or ASP2 fused with a mono-ubiquitin on its N-terminus (UASP2). C57BL/6 mice immunized intranasally with rSeV/dF expressing either ASP2 or UASP2 showed significantly suppressed parasitemia and could be protected from lethal T. cruzi challenge [Ref1345:Duan et al., 2009].
ASP1
Trypanosoma cruzi strain Sylvio X-10/4
1658194
1658195
AAB18265.1
CDD:271234
CDD:304605
5693
?
surface protein-1
6.46
67801.84
739
Non-viral sialidases; cd15482
>gi|1658194|gb|U74494.1|TCU74494 Trypanosoma cruzi surface protein-1 mRNA, complete cds
GGCACGAGCGGATCCAGCGGAAGGAGGAGGGAAGGAAGAGAGAGTGAGCCGCAGAGGTTCAACATGTCCC
GACATCACTTCTATTCCGCGGTGCTGCTTCTTGTCGTGATGATGTGCTGTGGATTTGGAGCTGCACACGC
TGTGGAAAGTAATTTGAGGGATGCGCAGATGCCGCAATGGGTTGATATTTTTGTCTCGGGTAAGACGCGG
GTGCTGGCAAAGGATGGGACTGAAGTCGGAGCGAGCGATTCGTTTGGCGCAGGCTCTCCTGTCATTGCTG
GCGGAGTGATGGCTGTGGTTACTACCGGCAATTTTTTACGTGATCCTGTAATATTCCTTTCTCAATCTGA
TGTTGTTGGGGGGTATTTCAACCCTGCGTGGGATTGGTCGTTCCTTGTCGCTAAGGTCAGTGAGGATACA
TGGAGAGCACACACTGTGTTTCATACAGCGAATGAAACGGAACTTGTGGGTGTTGCGCGCCTTCCGACAA
CCATTGGGAAGGGCAATAAGGTGTATCTCCTTGTGGAAAGCTATGAAAAGAAGTATGACGGCGCCGCGAA
GAAATGGACGACGGATGGCAAGGATATCAAACTGATTGTGGGTGACGCCAGGCCGTCCACGGGCAGAAGG
GAGAGTGGAACAATCATCTGGGGCGATCCCACATCGCTGTTACAACAGCTCACCCCAGAGACTCAAACTG
AGTTGAAGAAGCTTGCTCCCTTTGGTGGCGCTGGTGTTCTGATGGAGAATGGCACTCTCGTGTTTCCTTT
GTCGGGGACTAATGAACAGCGTGGGCATTCCAACAGGATCACTTACTCGACGGACGACGGCACAAACTGG
GTGTTTCCGGCGGGTACGCCCCCTGCGGAATGTGTTGGAATCAGCATCACCGAATGGGAGACGGGACAAA
TTCTCATGGTTACTGGATGCACGATTGGTCGCAAGGTGTACGAGTCGCGTGACATGGGGACAACGTGGAC
GGAGGCTGTCGGGACACTCCCAGGCGTGTGGGTCAACGCACGATCAGGAACTCGTTGGACTGTTGATTTG
TCTGTGGGATCTCTCATCACCGCGACCATTGAGGGAGTGAAGGTCATGCTGTACACTCATAAAAGATACC
GCACTTTGGGAGAAAAAGGAGAAGGCGCTCTATCTTTGTGTCACGGACAACAGCCGCATGTTTTGGGCTT
GGACCGATTTATGTGGAGAGTCTTTTGGAGTGAGACAGTTTCCAACAACCTGCTGCACTCGGATGGTGCG
TTGCACATTACAAGATTAACGTATACAGGAGCCGGCACAGTCATTTCACTTGCCCGGCTAACAAGGGAAC
TGGAGACAATCAAGTCCACCCTCAGTAATTGGAAAAAGCTGGACGCCTCCTTCTCCAAGTCGTCCACACC
CACAGCCGGTCTGGTTGGATTTTTGTCCAACGCGGCCAGTGATGACACGTGGCTTGACGATTACGGCTGC
GTGAATGCAAACGTGACGAGAGCAACGAAGGTTCACAACGGTTTTAAATTTATGGGGGCTGGATCCAAGG
CAGTGTGGCCCGTGAACACCTGGGAGGAAAATACTTACTACGGCTTTGTGAACCACGATTTCACTGTTGT
GGCGACGGTGGTCATCCACAAGGCTCCGAGTGAGAGCACTCCTCTGCTGGGTGCGGGTCTGGGAGACAAT
GACGGCACTAAGTTTATTGGGCTGTCGTACGATGCGAACCGTAATTGGGAGACAGTGTTCAGCGCCAAAA
AAACAGCATCGGGCAGCACTTGGGAGCCGGGGAAAGAATACCAAGTGGCGCTCATGCTGCAGGGCGCCAA
CAAGGGCTCAGTGTACGTGGATGCCAAGCTCGTGGGGAGCCCGGAGACGTTACCAACACCTGAGACGCGG
GGGGCTGAAATCACACATTTCTACATTGGGGGAGACGAGGGAGACAGCGGAAGCGATCTGACGGTGACGA
ATTCCTTTCTGTACAACCGCCCACTGAGTGAAGATGAACTAAAAATGGTCAAGAAGAAAGAGGACTCCGT
GCGTGGAGACGTGTCTCGGGTGCTCCCGCTGCTTCTGCTGGGGCTGTGGGGCCTTACGGGCCTTTACTGA
>AAB18265.1 surface protein-1 [Trypanosoma cruzi]
MSRHHFYSAVLLLVVMMCCGFGAAHAVESNLRDAQMPQWVDIFVSGKTRVLAKDGTEVGASDSFGAGSPV
IAGGVMAVVTTGNFLRDPVIFLSQSDVVGGYFNPAWDWSFLVAKVSEDTWRAHTVFHTANETELVGVARL
PTTIGKGNKVYLLVESYEKKYDGAAKKWTTDGKDIKLIVGDARPSTGRRESGTIIWGDPTSLLQQLTPET
QTELKKLAPFGGAGVLMENGTLVFPLSGTNEQRGHSNRITYSTDDGTNWVFPAGTPPAECVGISITEWET
GQILMVTGCTIGRKVYESRDMGTTWTEAVGTLPGVWVNARSGTRWTVDLSVGSLITATIEGVKVMLYTHK
RYRTLGEKGEGALSLCHGQQPHVLGLDRFMWRVFWSETVSNNLLHSDGALHITRLTYTGAGTVISLARLT
RELETIKSTLSNWKKLDASFSKSSTPTAGLVGFLSNAASDDTWLDDYGCVNANVTRATKVHNGFKFMGAG
SKAVWPVNTWEENTYYGFVNHDFTVVATVVIHKAPSESTPLLGAGLGDNDGTKFIGLSYDANRNWETVFS
AKKTASGSTWEPGKEYQVALMLQGANKGSVYVDAKLVGSPETLPTPETRGAEITHFYIGGDEGDSGSDLT
VTNSFLYNRPLSEDELKMVKKKEDSVRGDVSRVLPLLLLGLWGLTGLY
Protective antigen
CRP-10
Escherichia coli str. K-12 substr. MG1655
VO_0011297
947867
16131236
b3357
U00096
NP_417816
CDD:271234
CDD:290570
511145
3486119
3486751
+
DNA-binding transcriptional dual regulator CRP
8.46
22251.2
210
Also known as cap; csm; ECK3345; gurB
>NC_000913.3:3486119-3486751 Escherichia coli str. K-12 substr. MG1655, complete genome
CATGGTGCTTGGCAAACCGCAAACAGACCCGACTCTCGAATGGTTCTTGTCTCATTGCCACATTCATAAG
TACCCATCCAAGAGCACGCTTATTCACCAGGGTGAAAAAGCGGAAACGCTGTACTACATCGTTAAAGGCT
CTGTGGCAGTGCTGATCAAAGACGAAGAGGGTAAAGAAATGATCCTCTCCTATCTGAATCAGGGTGATTT
TATTGGCGAACTGGGCCTGTTTGAAGAGGGCCAGGAACGTAGCGCATGGGTACGTGCGAAAACCGCCTGT
GAAGTGGCTGAAATTTCGTACAAAAAATTTCGCCAATTGATTCAGGTAAACCCGGACATTCTGATGCGTT
TGTCTGCACAGATGGCGCGTCGTCTGCAAGTCACTTCAGAGAAAGTGGGCAACCTGGCGTTCCTCGACGT
GACGGGCCGCATTGCACAGACTCTGCTGAATCTGGCAAAACAACCAGACGCTATGACTCACCCGGACGGT
ATGCAAATCAAAATTACCCGTCAGGAAATTGGTCAGATTGTCGGCTGTTCTCGTGAAACCGTGGGACGCA
TTCTGAAGATGCTGGAAGATCAGAACCTGATCTCCGCACACGGTAAAACCATCGTCGTTTACGGCACTCG
TTA
>NP_417816.1 DNA-binding transcriptional dual regulator CRP [Escherichia coli str. K-12 substr. MG1655]
MVLGKPQTDPTLEWFLSHCHIHKYPSKSTLIHQGEKAETLYYIVKGSVAVLIKDEEGKEMILSYLNQGDF
IGELGLFEEGQERSAWVRAKTACEVAEISYKKFRQLIQVNPDILMRLSAQMARRLQVTSEKVGNLAFLDV
TGRIAQTLLNLAKQPDAMTHPDGMQIKITRQEIGQIVGCSRETVGRILKMLEDQNLISAHGKTIVVYGTR
Protective antigen
A complement regulatory protein (CRP) of Trypanosoma cruzi was evaluated as a vaccine candidate in a murine model of experimental T. cruzi infection. Recombinant CRP derived from an Escherichia coli expression system and a plasmid encoding the full-length crp structural gene under the control of a eukaryotic promoter were used to immunize BALB/c mice. Immunization with both protein and DNA vaccines resulted in a Th1-type T-cell response, comparable antibody titers, and similar immunoglobulin G isotype profiles. Only mice immunized with the crp DNA plasmid produced antibodies capable of lysing the parasites in the presence of complement and were protected against a lethal challenge with T. cruzi trypomastigotes [Ref1354:Sepulveda et al., 2000].
Cruzipain
Trypanosoma cruzi
VO_0011293
3550848
71663165
AAHK01000135
XP_818579
CDD:185513
CDD:214853
CDD:278538
CDD:239068
CDD:288946
5693
Unknown
102406
103809
+
cruzipain
6.01
45629.84
467
internal copy from a tandem array
>NW_001849391.1:102406-103809 Trypanosoma cruzi strain CL Brener 1047053516253 genomic scaffold, whole genome shotgun sequence
AATGTCTGGCTGGGCGCGTGCGCTGTTGCTCGCGGCCGTCCTGGTCGTCATGGCGTGCCTTGTCCCCGCG
GCGACGGCGAGCCTGCATGCGGAGGAGACGCTGACGTCGCAATTCGCAGAATTCAAGCAGAAGCATGGCA
GGGTGTACGAGAGCGCCGCGGAGGAGGCGTTCCGCCTGAGCGTGTTCAGGGAGAACCTGTTTCTTGCGAG
GCTGCACGCCGCGGCAAACCCACACGCGACCTTCGGCGTCACGCCCTTCTCGGACCTCACGCGCGAGGAA
TTCCGGTCCCGCTACCACAACGGCGCGGCGCACTTTGCGGCGGCGCAGGAGCGCGCGAGAGTGCCGGTGA
AGGTGGAGGTAGTTGGCGCGCCCGCGGCAGTGGATTGGCGTGCGAGAGGCGCCGTGACAGCCGTCAAGGA
CCAGGGCCAATGCGGTTCGTGCTGGGCCTTCTCCGCCATTGGTAACGTTGAGTGCCAGTGGTTTCTTGCC
GGCCACCCGCTGACGAACCTGTCGGAGCAGATGCTCGTGTCGTGCGACAAAACGGACTTTGGCTGCAGTG
GTGGCCTGATGAACAACGCCTTTGAGTGGATTGTGCAGGAGAATAACGGCGCCGTGTACACGGAGGACAG
CTACCCTTATGCGTCGGGCGAGGGGATATCGCCGCCGTGCACGACGTCAGGCCACACGGTGGGTGCCACG
ATTACCGGTCACGTTGAATTACCTCAGGACGAGGCCCAAATAGCCGCATGGCTTGCAGTCAATGGCCCGG
TTGCCGTTGCCGTCGACGCCAGCAGCTGGATGACCTACACGGGCGGCGTTATGACGAGCTGCGTCTCCGA
GCAGCTGGATCACGGCGTTCTTCTCGTCGGCTACAATGACAGCGCCGCAGTGCCGTACTGGATCATCAAG
AACTCGTGGACCACGCAGTGGGGCGAGGAAGGCTACATCCGCATTGCAAAGGGCTCGAACCAGTGCCTTG
TCAAGGAGGAGGCGAGCTCCGCGGTGGTCGGTGGTCCCGGACCCACTCCCGAGCCAACCACCACGACAAC
CACAAGTGCCCCAGGACCGTCCCCATCGTACTTTGTGCAGATGTCCTGCACTGACGCTGCGTGCATTGTC
GGGTGCGAGAACGTGACGTTACCGACCGGTCAGTGTCTCCTGACCACCAGCGGCGTCTCTGCCATTGTCA
CGTGCGGTGCTGAGACTCTCACAGAAGAAGTCTTCCTTACGAGTACGCACTGCAGCGGCCCATCGGTGAG
GTCCTCTGTTCCTCTCAACAAATGCAACCGGCTTTTAAGAGGCTCCGTTGAGTTCTTCTGCGGCTCCAGC
TCCAGTGGCCGACTGGCCGACGTGGACAGGCAGCGTCGCCATCAGCCATACCACAGCCGTCATCGCCGCC
TCTG
>XP_818579.1 cruzipain precursor, putative [Trypanosoma cruzi]
MSGWARALLLAAVLVVMACLVPAATASLHAEETLTSQFAEFKQKHGRVYESAAEEAFRLSVFRENLFLAR
LHAAANPHATFGVTPFSDLTREEFRSRYHNGAAHFAAAQERARVPVKVEVVGAPAAVDWRARGAVTAVKD
QGQCGSCWAFSAIGNVECQWFLAGHPLTNLSEQMLVSCDKTDFGCSGGLMNNAFEWIVQENNGAVYTEDS
YPYASGEGISPPCTTSGHTVGATITGHVELPQDEAQIAAWLAVNGPVAVAVDASSWMTYTGGVMTSCVSE
QLDHGVLLVGYNDSAAVPYWIIKNSWTTQWGEEGYIRIAKGSNQCLVKEEASSAVVGGPGPTPEPTTTTT
TSAPGPSPSYFVQMSCTDAACIVGCENVTLPTGQCLLTTSGVSAIVTCGAETLTEEVFLTSTHCSGPSVR
SSVPLNKCNRLLRGSVEFFCGSSSSGRLADVDRQRRHQPYHSRHRRL
Protective antigen
To study the protective effects in vivo of cruzipain-specific Th1 responses against systemic T. cruzi challenges, mice were immunized with recombinant cruzipain plus interleukin 12 (IL-12) and a neutralizing anti-IL-4 MAb. These immunized mice developed potent cruzipain-specific memory Th1 cell responses and were significantly protected against normally lethal systemic T. cruzi challenges. To study whether cruzipain could induce mucosal immune responses relevant for vaccine development, recombinant attenuated Salmonella enterica serovar Typhimurium vaccines expressing cruzipain were prepared. BALB/c mice immunized with salmonella expressing cruzipain were significantly protected against T. cruzi mucosal infection [Ref1349:Schnapp et al., 2002].
G2
Trypanosoma cruzi
VO_0011299
3543901
71424025
AAHK01000586
XP_812654
5693
Unknown
46754
47725
+
protein G2
7.16
33715.38
323
>NW_001849278.1:46754-47725 Trypanosoma cruzi strain CL Brener 1047053517025 genomic scaffold, whole genome shotgun sequence
GATGGCGAGGCGAGCGGCACTGCGATGGTGGCCGGCGTGCGGGCCATTGGATTTATTTTTGAAAAACGAG
GAAGTCAAGAATCCTAGCTTGTGTGTGCATAAGAATGATTTTGGTCAAATGGTGTTGAGTGGCATGGGAG
AATTACATCTTGAAATTGTCATGTCCCTCTTGGAGCACGATTATAAACTAAAGTGTCGACTACTACGTGC
CATCGTAGAATATCGTGAGGTAGTCCTTGAGGCAGTGGAGCTCCTGCATGGTATTGGGATGTACAATGAG
CTCCCATACGTTGAGTGTTCGCTGCGACTCCAGCCACTACTTGAGGAAGATGGCTTCTGCGATCCAGTTC
AATATTGTTCCTTTGTTCTTGACGAGACGTTGACGGAGAAATATCTTGCTGGAGCCGCTGGTTCCCGTAA
TGATCGACGTCGCCGCATGGAGGATCACCACCGTAATGTGAAGGAGGAACTACGAATAAACACCGATGTT
TTTTCTCGCGCAGTCACCGATTGCTCTCACATGGGTCCCCTTGCCGGTTTGCCTCTCCACGGCGTGCGGG
TCGCTTTGCTGGAATTCAAAAAGCTTGGTGGCACGCAGCTGTCGGAGGGCCCTCTACAGCAGGCCGCTCG
TTCTCTTGTATTGGAGCTGTTTCGCTCCGTTTCCAAGGCCAATCTTGCCACGATGGAGCCAATGATGGAG
GTGGAGGTGCACCTCTCGGAGGCAGCCTACATTGGTGGTGTTGTGAGCTCTCTGAGCGAGCGTAAGGCCA
TTGCGGTGGACATTCAAGATGATGGGAGGTCGGTGAAAGCAATCGTCCCGATGCGAAACATAGTTCGCTA
CACAATGGAACTTTGGAAGGCGGTGAAGGGGCATGCCAGTCTGTACGCACGCTTGCACCACTACCGTGTA
ATTGAAGAAAAGGCTGTCCTCTCGCGAATCATGAAGAATTTGGGCATTTACGAAGGCCATTG
>XP_812654.1 elongation factor G2-like protein, putative [Trypanosoma cruzi]
MARRAALRWWPACGPLDLFLKNEEVKNPSLCVHKNDFGQMVLSGMGELHLEIVMSLLEHDYKLKCRLLRA
IVEYREVVLEAVELLHGIGMYNELPYVECSLRLQPLLEEDGFCDPVQYCSFVLDETLTEKYLAGAAGSRN
DRRRRMEDHHRNVKEELRINTDVFSRAVTDCSHMGPLAGLPLHGVRVALLEFKKLGGTQLSEGPLQQAAR
SLVLELFRSVSKANLATMEPMMEVEVHLSEAAYIGGVVSSLSERKAIAVDIQDDGRSVKAIVPMRNIVRY
TMELWKAVKGHASLYARLHHYRVIEEKAVLSRIMKNLGIYEGH
Protective antigen
The vaccine efficacy of a putative candidate antigen against T. cruzi infection and disease in a mouse model. C57BL/6 mice vaccinated with a T. cruzi G2-encoding plasmid and cytokine (interleukin-12 and granulocyte-macrophage colony-stimulating factor) expression plasmids elicited a strong Th1-type antibody response dominated by immunoglobulin G2b (IgG2b)/IgG1 isotypes. The dominant IgG2b/IgG1 antibody response was maintained after a challenge infection and was associated with 50% control of the acute-phase tissue parasite burden and an almost undetectable level of tissue parasites during the chronic phase, as determined by a sensitive T. cruzi 18S rRNA gene-specific real-time PCR approach [Ref1355:Bhatia and Garg, 2008].
par1
VO_0011301
2209137
CDD:282940
5693
?
paraflagellar rod component
4.95
64852.11
665
Paraflagellar rod protein; pfam05149
>AAC32021.1 paraflagellar rod component [Trypanosoma cruzi]
MTVYHEQFALVPPQYPRRAVQEAENHRALAALYELVENAIATAENYVAYTEGRLVPLSSRGSELLAASKE
LRERYRHEAPCGWTEQKVMQHCEQEVTVEEMAELLLRPPLDVAGIRSILRTLQETRTQLPRGRFLLMRDN
LSALKPHQPPDLARDLSDVCGALYEIQYVDLMAELRAELSELDGERDKVQEKLKDAIHLYERAVAKGDVV
EVERAHRQLIAARYEFVNACAKLMHQILGEDMASQESGFAAEMEALRRDAADSISRFAEALHERRQAFRN
DLHNCDKKRLEEDGNHQKCLEVYNAEERETAAQIGQIVEQKKKLVEELRQKARELRDITLKQKEMVEAQV
RAKRAEEERVTAYNEFVNMEEQQKHRLLRCLAYFDGMEELTADLRSYVDEMVTRIPQQNLRQVLDQLNDI
EAEVFMNAYGGFVSCCGELTVKKMHRLDTLERQARLLEHNRDSAMESLDPNMSNYRLELDDIIEQMKGVS
GVINALNATQDAGEQLFQSVEKGVLAKYERSGTPFVHPLQEYGIKSVEERNRFVDRSMHYVENEERKVLE
KRNVLNRMRQAVEEDEAATESAIRNLNEEPAAPEY
Protective antigen
C57BL/6 mice were immunized s.c. with recombinant PFR-1 (PAR1) protein co-adsorbed to alum with rIL-12. rPFR-1 immunized animals were able to successfully resolve parasitemia by day 30 p.i., with the peak parasitemia occurring between days 17 and 21 p.i. [Ref1357:Luhrs et al., 2003].
protein G4
Trypanosoma cruzi
VO_0011298
52424038
5693
?
protein G4
10.06
10324.13
137
>AAU47268.1 protein G4 [Trypanosoma cruzi]
MSAKAPPKTLHQVRNVAYIFAAWAGLQKGFAEKSANDKMWVEHQRRLRQENAKRQHAAHALEELKQDEEL
ERSIPTIVPKELHELVKALEK
Protective antigen
The vaccine efficacy of a putative candidate antigen against T. cruzi infection and disease in a mouse model. C57BL/6 mice vaccinated with a T. cruzi G4-encoding plasmid and cytokine (interleukin-12 and granulocyte-macrophage colony-stimulating factor) expression plasmids elicited a strong Th1-type antibody response dominated by immunoglobulin G2b (IgG2b)/IgG1 isotypes. The dominant IgG2b/IgG1 antibody response was maintained after a challenge infection and was associated with 90% control of the acute-phase tissue parasite burden and an almost undetectable level of tissue parasites during the chronic phase, as determined by a sensitive T. cruzi 18S rRNA gene-specific real-time PCR approach [Ref1355:Bhatia and Garg, 2008].
Tc00.1047053434931.10
Trypanosoma cruzi strain CL Brener
VO_0011300
3532027
71398801
Tc00.1047053434931.1
AAHK01004051
XP_802646
353153
93194
93988
+
paraxonemal rod protein PAR2
6.21
29966.04
264
>NW_001849495.1:93194-93988 Trypanosoma cruzi strain CL Brener 1047053517073 genomic scaffold, whole genome shotgun sequence
NCAGGACGAGGCGTGGCGCCGCATCCAGGAGCTCGAGCGTGTCCTGCAGCGTCTGGGGACGGAGCGATTT
GAGGAGGTGAAGCGCCGCATTGAGGAGAACGACCGCGAGGAGAAGCGCAAGGTGGAGTACCAGCAGTTCC
TGGATGTATGTGGGCAGCACAAGAAGCTGCTGGAGCTGTCGGTGTACAACTGCGACCTGGCGATGCGATG
CATCGGGATGATGGAGGAGCTGGTGGCGGAGGGCTGCAGCGCAATCAAGTCGCGCCACGACAAGACGAAC
GAGGAGCTGGGGGACCTGCGGCTGCAGGTGCATCAGGAGTACCTGGAGGCGTTCCGCCGCCTGTACAAGA
CGCTGGGCCAGCTGGTGTACAAGAAGGAGAAGCGCCTGGAGGAGATTGACCGCAACATCCGCACGACGCA
CATTCAGCTGGAGTTTGCCATCGAGACGTTTGACCCGAACGCGAAGAAGCACTCGGACGCCAAGAAGGAG
CTGTACAAGCTCCGCGCGCAGGTGGAGGAGGAGCTGGAGATGCTGAAGGACAAGATGGCGCAGGCGCTGG
AGATGTTTGGCCCGACCGAGGACGCGCTGAACCAGGCCGGCATTGAGTTTGTGCATCCCGCCGAGGAGGT
GGAGGACGGCAACCTGACCCGCCGCAGCAAGATGGTCGAGTACCGTGCCCACCTGGCGAAGCAGGAGGAG
GTGAAGATTGCGGCGGAGCGCGAGGAACTGAAGCGCTCCAAGACACTGCAGAGCCAGCAGTACCGCGGCA
AGACGGTGCAGCAGATCACACAGTA
>XP_802646.1 paraxonemal rod protein PAR2, partial [Trypanosoma cruzi strain CL Brener]
QDEAWRRIQELERVLQRLGTERFEEVKRRIEENDREEKRKVEYQQFLDVCGQHKKLLELSVYNCDLAMRC
IGMMEELVAEGCSAIKSRHDKTNEELGDLRLQVHQEYLEAFRRLYKTLGQLVYKKEKRLEEIDRNIRTTH
IQLEFAIETFDPNAKKHSDAKKELYKLRAQVEEELEMLKDKMAQALEMFGPTEDALNQAGIEFVHPAEEV
EDGNLTRRSKMVEYRAHLAKQEEVKIAAEREELKRSKTLQSQQYRGKTVQQITQ
Protective antigen
C57BL/6 mice were immunized s.c. with recombinant PFR-2 (PAR2) protein co-adsorbed to alum with rIL-12. rPFR-2 immunized animals were able to successfully resolve parasitemia by day 30 p.i., with the peak parasitemia occurring between days 17 and 21 p.i. [Ref1357:Luhrs et al., 2003].
Tc24 (Obselete)
Trypanosoma cruzi
ABA62611
CDD:238008
CDD:290234
5693
Tc24 protein
4.82
18914.11
239
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to...; cd00051
>ABA62611.1 Tc24 protein, partial (kinetoplast) [Trypanosoma cruzi]
RKEAWERIRQAIPREKTAEAKQRRIELFKKFDKNETGKLCYDEVHSGCLEVLKLDEFTPRVRDITKRAFD
KARALGSKLENKGSEDFVEFLEFRLMLCYIYDFFELTVMFDEIDASGNMLVDEEEFKRAVPKLEAWGAKV
EDPAALFKELDKNGTGSVTFDEFAAWA
Protective antigen
[Ref5052:Barry et al., 2016]
Tc24 from Trypanosoma cruzi
Trypanosoma cruzi
77167273
CDD:238008
CDD:290234
5693
?
Tc24 protein
4.82
18914.11
239
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to...; cd00051
>ABA62611.1 Tc24 protein, partial (kinetoplast) [Trypanosoma cruzi]
RKEAWERIRQAIPREKTAEAKQRRIELFKKFDKNETGKLCYDEVHSGCLEVLKLDEFTPRVRDITKRAFD
KARALGSKLENKGSEDFVEFLEFRLMLCYIYDFFELTVMFDEIDASGNMLVDEEEFKRAVPKLEAWGAKV
EDPAALFKELDKNGTGSVTFDEFAAWA
Protective antigen
Tc80
Trypanosoma grayi
20379487
686630079
DQ04_00541100
JMRU01000054
XP_009307485
71804
17527
19620
+
5.23
73272.55
697
>NW_008825673.1:17527-19620 Trypanosoma grayi strain ANR4 Tgr_54_V1, whole genome shotgun sequence
AATGCGCTCACTCTACCCGCTGGCCAGGAGGTCCATGGCGGCCTACAAGATACACAATGTTACAGTGCCT
GAGCCGTACGACTACCTCGAAGACCCCCAGAACGATGAAACAAAGTCATTTGTGCAGGCACAAAACGTTT
TCTTCGAGGAATACCTCTCAGCCGATGCTGAACTCCGCGAAAATTTTTTTGAGTGTATCTCAGCGTCGCA
AAATTACCCCCGAACGTCATGCCCAAGCTTTCGTCACGGTCAATACTACTTCTACCACAACACGGGCCTT
CAGAACCAGAGTGTGTTAATGCGTGCAAAGAGCCTAACCAACGCGACATCCAGCGTCTTCCTCGATCCTA
ACACTATGAGTGGCGATGGTACTACTGCGCTCAAGGCCACAGCCTGGAGTGAGGACGAGTCGCTGCTTGC
GTACAGTATTAGCGAAAAGGGCAGCGATTGGCAAAGCATTCGCGTGCGGTGTGCCGACACAGCGGAGGAT
ACTGCGGACAATATTGAGTGGGCCAAGTTCACAGGTATTGCGTGGTGGCATGACACCGGGTTCTTCTACA
CACGCTATCCCGCCCTCCAGAGTAATGTGGACAAGGGTGCAGAAACTGACACGGCGCAGGACCCTTTTAT
CTGTTTCCACCGCCTGGGCCGCCCGCAGGCAGAGGACGTGGCGATTCTTGCCGTGCCAGAGCACCCGCAG
TGGAGCCTGGGGGCTGAGGTGTCCGATTGTCAATCGTATATCATTGTCTCACTGTTCGACGGCTGTGAAC
CTCGGAACCTTGTTTGGATTGCAGAGCTGCCCACCAGTGAGGAAGGAATCGGGTCCACACCGCTGAAGTT
CACGAAGTTGGTGAATGAGTTTGTTGGCAAGTATGACTACTTGGGAAATGATGGAGTAAAGTTCTATTTT
GTCACCACCCGCGACGCGCCGCGGAAAAAGATCGTCTCCATAGACATTTGTAACGGCGACGAGGATGTTG
TCGTCGAAGAACAGCGTTCCGTGTTAAACCACGCTGCACTCGTAAAGAACACGCTTTTACTCACCTACCT
CGAGGACGTGAAGGATGTTCTGTACTTCCGCCGTCTTGATGAGTCTACGCCGAATGCAATTCCTTTGCCG
ATTGGTACGATTGCCTCCCTCTTTGTCGACCGGAAAAAAGACTTTGTTTCTTTCAAGATGACGTCCTTCC
TTCTCCCTGGGCGTAGTTTCGTCATGGACATCAACGACCCACTGGGATCACTTTGCATCTACAAGGACGA
TACGGTTGAAGGTCTATCCGCCGACGACTTCGTCACGGAGCAGGTGTTTTATAACTCAGCGGATGGAACG
CGAATTCCAATGTTTATTATCCACAGAAAGGGTCTTGCTACACCAGAGTCCCCGCTTCTTCTTTACGGCT
ACGGTGGTTTTAATATTTCGCTGACGCCGGGGTTTAGCTCCTCGCGAGTGGTGTTCCTCCAGAAACTCGG
TGGTGTGCTGGCGATACCGAATATCCGAGGCGGCGGTGAATACGGTGAAGAGTGGCACGACGCTGGTAGG
CAAGCCCACAAGCAAAATTGCTTCACAGATTTCATTGAGGCCGCTAGGTTTTTACACAGTCATAGCTACG
GCTCCCCTCAGACGACGGCTATTATGGGCGGATCCAATGGTGGGCTTCTGGTCGCGGCGGCTGCGAATCA
AGCGCCGGAGCTTTTTAGCTGTGTTGTCTGCCAAGTGGGAGTGCTGGATATGTATAAATTCCACAAGTTT
ACCATTGGACACGCGTGGAAATCAGATTACGGTGACCCAGAGAAGGAAGAGGATTTCAAGATTTTACAGC
GGTATAGTCCGATTCACAACATCCGGTCTGGTATTAAATATCCTGCCATTCTGGTGGTGACAGGCGACCA
TGACGACCGTGTTGTGCCTCTCCATTCGCTAAAATACCTTGCGACGCTCCAGCATGCCAACCCGACGGAA
GGGGGACCTTTTTTGGCGCGCGTAGAGGTAGCCGCCGGCCATGGTGCTGGCAAACCCACCAGTAAAATCA
TGCGCGAGGCGGGCGACATTTACACCTTTATCACCAAGAGTATTCACGCGGCGTGGAAGGAGTG
>XP_009307485.1 putative prolyl oligopeptidase, putative,serine peptidase clan SC, family S9A [Trypanosoma grayi]
MRSLYPLARRSMAAYKIHNVTVPEPYDYLEDPQNDETKSFVQAQNVFFEEYLSADAELRENFFECISASQ
NYPRTSCPSFRHGQYYFYHNTGLQNQSVLMRAKSLTNATSSVFLDPNTMSGDGTTALKATAWSEDESLLA
YSISEKGSDWQSIRVRCADTAEDTADNIEWAKFTGIAWWHDTGFFYTRYPALQSNVDKGAETDTAQDPFI
CFHRLGRPQAEDVAILAVPEHPQWSLGAEVSDCQSYIIVSLFDGCEPRNLVWIAELPTSEEGIGSTPLKF
TKLVNEFVGKYDYLGNDGVKFYFVTTRDAPRKKIVSIDICNGDEDVVVEEQRSVLNHAALVKNTLLLTYL
EDVKDVLYFRRLDESTPNAIPLPIGTIASLFVDRKKDFVSFKMTSFLLPGRSFVMDINDPLGSLCIYKDD
TVEGLSADDFVTEQVFYNSADGTRIPMFIIHRKGLATPESPLLLYGYGGFNISLTPGFSSSRVVFLQKLG
GVLAIPNIRGGGEYGEEWHDAGRQAHKQNCFTDFIEAARFLHSHSYGSPQTTAIMGGSNGGLLVAAAANQ
APELFSCVVCQVGVLDMYKFHKFTIGHAWKSDYGDPEKEEDFKILQRYSPIHNIRSGIKYPAILVVTGDH
DDRVVPLHSLKYLATLQHANPTEGGPFLARVEVAAGHGAGKPTSKIMREAGDIYTFITKSIHAAWKE
Protective antigen
TcG4
Trypanosoma grayi
20379573
686630251
DQ04_00581060
JMRU01000058
XP_009307571
71804
9137
9412
-
9.76
9627.25
91
>NW_008825677.1:9137-9412 Trypanosoma grayi strain ANR4 Tgr_58_V1, whole genome shotgun sequence
ACTACTTCTCAAATGCCTTAACAAGCTCGTGAAGCTCCTTGGGAACGATCTCAGGAATGCTTCCTTCTGT
CTCCGCACCACGATTCGCCTCCTGCAAAGCGTGTGCCGCAAGCTGCTTTTCAGCGTTCTGCTGGCGTACA
TGGCGTTGGTGTTCAACCCACAGTTTATCGTTGGCCGACTTTTCCGCGAAGCCCTTCTGGAGGCCTGCCC
ATGCGGCAAAGATGTACGCCACGTTGCGAACCTGATGGAGTGTTTTTGGAGGGGCCTTGGCCGACA
>XP_009307571.1 protein G4 [Trypanosoma grayi]
MSAKAPPKTLHQVRNVAYIFAAWAGLQKGFAEKSANDKLWVEHQRHVRQQNAEKQLAAHALQEANRGAET
EGSIPEIVPKELHELVKAFEK
Protective antigen
trans-sialidase(TsF) from Trypanosoma cruzi
Trypanosoma cruzi strain CL Brener
3537653
71410253
AAHK01001396
XP_807431
353153
35836
38658
-
6.46
91068.77
940
>NW_001849266.1:35836-38658 Trypanosoma cruzi strain CL Brener 1047053516005 genomic scaffold, whole genome shotgun sequence
ATCAGAAAAAAACTGCCGTAAAGAACACGTGCAGCAGCAAAGCACACGCACACAGAAGAAGCCCTCCGCC
CGAAAAGGCCGAAAGTGCAGCGCCATCGGGCAAAATCAAAACCGTACCATTGGCACCGTTGCCAGCGGGA
GTTGAGGGCGTACTGTGAGCACTGCTGTCAGCGGGAGTTGAGGGCGTACTGTGGGCACTGCTGTCAACGG
GAGTCGAGGGCGTACCGTGGGCACTGCTGTCAACGGGAGTCGAGGGCTTACCGTGGGCACTGCTGTCAAC
GGGAGTCGAGGGTGTACCGTGGGCACTGCTGTCAACGGGAGTCGAGGGTGTACCGTGGGCACTGCTGTCA
ACGGGAGTCGAGGGCGTACCGTGGGCACTGCTGTCAACGGGAGTCGAGGGTGTACCGTGGGCACTGCTGT
CAACGGGAGTCGAGGGCGTACCGTGGGCACTGCTGTCAACGGGAGTCGAGGGTGTACTGTGGGCACTGCT
GTCAACGGGAGTTGAGGGCGTAGCGTGGGCACTGCTGTCAACGGTAGTTGAGGGCGTACCGTGGGCACTG
CTGTCAACGGGAGTTGAGGGCGTACCGTGGGCACTGCTGTCAACGGTAGTTGAGGGCGTACCGTGGGCAC
TGCTGTCAACGGGAGTCGAGGGCGTACCGTGGGCACTGCTGTCAACGGGAGTCGAGGGTGTACTGTGGGC
ACTGCTGTCAACGGGAGTTGAGGGCGTAGCGTGGGCACTGCTGTCAACGGGAGTCGAGGGTGTACCGTGG
GCACTGCTGTCAACGGGAATCGAGGGCGTACCGTGGGCACTGCTGTCGCTGCTGCTGTCCATGTGTGCTT
CCGTGCCAATCAGGTCCTGGCTCAAGAACAAGGTCCTGATCTCCTCGGCATTCAGCTGACGGTTGTAAAG
AAGAACATTATTCACCGTCACGTGGCTTATGGTTGGCATATCACTCCTTTTATACCCGCCAACGTAGAAG
TGGGAGATGTCAGGCGTCCTCCCGTCTGGCACAACGGTCTGCCCTGAACCCTCCAGAGGTTCTCCATCAA
TGTACACGGAGCCAATTTTATTCGACATCGTAAGAACCACGTGGTACCTCTTACCCGTCTCCCACGATCC
CGTCGGCGTCACCGGCGTTGATCCGTATATTGGCTGCCACTGGTGCTTCTCGTCGTACGAGAGCCCCAGG
AGTTTTTTGCCACCAGAAGAGTCCAGGCTCGCACCCAGCAGAGGAGTCGCGTCCCTCGGAGCCTCGTGAA
TCGTCACCGACGCCACCAGCGTGAACGCGTGGTTTGCAAAACGATACCGTTGATTCTGCCCCTGCTGGCT
CACCGGCCAAAGCGCCCCTCCGCCAACCCCCGCAAACTTCAAACCGTTCGGAACCCTCTCCGCATTTGCC
GTGCTCGCGTTGACGCAGCGGTACGCATCCTCCCATACGTTTTGGGAGGCATTGCCGGACAAAAAGCCAA
CAAGACCAACCGTGGTGACAGCGGGACCACAACCACGCTCTGACGACGAAGCGGCTGGATCAGCAGGGGT
GCAAATGCTGGACAGGTGGCTGTCCCAATTCTTCCAGGACTGCAGCACTGATTTAATGATCCGTAGCTCG
CCAACCAGGCGTGCAAAAACAAGGCTGTACACCTCGTTAGTGTTGATCTCATGCAAACAGTACAGCTTAT
CATCCTTGTACAGGACGGAGCTGTAGGCGGAATTTTCATCACCAATGGATACTTGCCCAACGTTATAAAT
GCGCTGGTTATCCGTCAGCCAGAGGTTCAGTCGGTCGCGCAGCCACCTTCCCTTAAAATTCAGCGGGTGT
GTGAAGAGCATCACACGCATTCCTTCGATGGTCACGGCAGTGAAGCTGCTCTGACTGCCGGGCTGGTCCG
ATTTTGGTGAGGGGCCCCACACACGCGAGAGCGTGCCGACAGCCTCCACCCACGTATTCCCCATGTCACT
GGACTCGTACACCAGACGGCGTGTCCAGTCAACTCGGGTGTTTATGATGAGCTTCCCCTCCCACTCAAGG
GCCACAGGTTCAGAGCAGCCAAAATCACTCCTGCCCTTCCCAAACTTCCACGTCTTGCCCTCGTCTTCCG
AGTAGAAGATCTTGGAAAAAACTTGCTTCTTTTTGTTCGTAACCTGCACAGGGTACACAAGATTCCCGTT
GGACGCCACAATGGCAACACCCGCACCGCCAAGAAATTGATTTGTGTGCATTCCTTCCATTTCTGCCGGA
AAAAACTTCTTCAGTGACACGGGGCTCCCCCATTTGATACTCGCAGTTGTCTTGCCGCCCGCAGTGGACT
TCGTGACCTCACCAACGGCAAGCAGAATATCCCAGTCTCTCGCATCACCATGCGACGTCCAGTAGCTTCT
CGAACTATTGTAGCTTCCAACCAGGACGTAAAGCTTGTTGCCCTTCACAATCACTGTGGGATCCACCACA
CGAGAAACAGACGATGCACGACTGTTCTTGATGGCAATTTGGGTCTCCCACGTCTCCCCATCGTCCACGC
TGTACTTCGCCACCGTATCAATGAGGGAGTTGTCATTGGATGTTTCGTAGCGAGCGTCCGCGATGGCAAC
CATCACCCCGTCCACATTAACAAGGGCGGGGAGGCGGAACGAGTGGACAACCCGCTCGGTGACTTTGCCG
TCCTTTTCAAATGGCACCTTCGAGCTTTGCCGCTTAAACAGCTCAACTCGGCTCGATTCGGGTGCCAGGG
CATGCGCGGGCTCGCTGGGGCAGAGCGCAAGAAGAAGCGGCACGAAAAACATTAGCCAGAACATCCTACT
GGCCCCAACGACTGTTTTCCCCA
>XP_807431.1 trans-sialidase [Trypanosoma cruzi strain CL Brener]
MGKTVVGASRMFWLMFFVPLLLALCPSEPAHALAPESSRVELFKRQSSKVPFEKDGKVTERVVHSFRLPA
LVNVDGVMVAIADARYETSNDNSLIDTVAKYSVDDGETWETQIAIKNSRASSVSRVVDPTVIVKGNKLYV
LVGSYNSSRSYWTSHGDARDWDILLAVGEVTKSTAGGKTTASIKWGSPVSLKKFFPAEMEGMHTNQFLGG
AGVAIVASNGNLVYPVQVTNKKKQVFSKIFYSEDEGKTWKFGKGRSDFGCSEPVALEWEGKLIINTRVDW
TRRLVYESSDMGNTWVEAVGTLSRVWGPSPKSDQPGSQSSFTAVTIEGMRVMLFTHPLNFKGRWLRDRLN
LWLTDNQRIYNVGQVSIGDENSAYSSVLYKDDKLYCLHEINTNEVYSLVFARLVGELRIIKSVLQSWKNW
DSHLSSICTPADPAASSSERGCGPAVTTVGLVGFLSGNASQNVWEDAYRCVNASTANAERVPNGLKFAGV
GGGALWPVSQQGQNQRYRFANHAFTLVASVTIHEAPRDATPLLGASLDSSGGKKLLGLSYDEKHQWQPIY
GSTPVTPTGSWETGKRYHVVLTMSNKIGSVYIDGEPLEGSGQTVVPDGRTPDISHFYVGGYKRSDMPTIS
HVTVNNVLLYNRQLNAEEIRTLFLSQDLIGTEAHMDSSSDSSAHGTPSIPVDSSAHGTPSTPVDSSAHAT
PSTPVDSSAHSTPSTPVDSSAHGTPSTPVDSSAHGTPSTTVDSSAHGTPSTPVDSSAHGTPSTTVDSSAH
ATPSTPVDSSAHSTPSTPVDSSAHGTPSTPVDSSAHGTPSTPVDSSAHGTPSTPVDSSAHGTPSTPVDSS
AHGTPSTPVDSSAHGKPSTPVDSSAHGTPSTPVDSSAHSTPSTPADSSAHSTPSTPAGNGANGTVLILPD
GAALSAFSGGGLLLCACALLLHVFFTAVFF
Protective antigen
TS
Trypanosoma cruzi
VO_0011294
258547365
CDD:271234
CDD:304605
5693
?
trans-sialidase
7.26
32935.95
385
Non-viral sialidases; cd15482
>ACV74334.1 trans-sialidase, partial [Trypanosoma cruzi]
THPLNFKGRWLRDRLNLWLTDNQRIYNVGQVSIGDENSAYSSVLYKDDKLYCLHEINTNEVYSLVFARLV
GELRIIKSVLQSWKNWDSHLSSICTPADPAASSSERGCGPAVTTVGLVGFLSGNASQNVWEDAYRCVNAS
TANAERVPNGLKFAGVGGGALWPVSQQGQNQRYRFANHAFTLVASVTIHEVPSVASPLLGASLDSSGGKK
LLGLSYDEKHQWQPIYGSTPVTPTGSWETGKRYHVVLTMANKMGSVYIDGEPLEGSGQTVAPDERTPDIS
HFYVGGYKRSDMPTISHVTVNNVLLYNRQLNAEEIRTLFLSQ
Protective antigen
To develop a vaccine strategy taking advantage of activated CD8(+)T cells,a DNA vaccine, designated pGFP-TSA1, encoding a fusion protein linking GFP to a single CTL epitope of TSA1(TS), a leading candidate for vaccine against T. cruzi was constructed. C57BL/6 mice vaccinated with this plasmid showed suppressed parasitemia and prolonged survival. Vaccination with pGFP-TSA1 enhanced epitope-specific cytotoxicity and IFN-gamma secretion by CD8(+)T cells [Ref1350:Chou et al., 2008].
TSA-1
VO_0011296
162315
CDD:271234
CDD:290570
CDD:304605
CDD:281915
5693
?
trypomastigote surface glycoprotein
4.51
84400.87
916
Non-viral sialidases; cd15482
>AAA30259.1 trypomastigote surface glycoprotein [Trypanosoma cruzi]
MSRRHFYSAVLLLLLVVMVCGGSGAAHAVERNSGDLQLPQEIAMLVPNKTQVVPKSGGEGKVKDIFASPA
LVRAGGVMIAFVEGRTKNKLFPEVIDLSSSDIVAGYIKAPETWQSLVAEVTKEYWQAHTVLESANNSNHR
VGVARLPTGITRGNKVFLLVGSYEERREIDDYIWKAEAWNIKVIEGEATQSTEVQPTQPINWSEPKPLFQ
TDSPNNKGDLKEFLGGGGSGIVMGNGTLVFPLTAKDESNKVFSLITYSTDDGQKWEIPGGVSSVACRSPR
VTEWEEGTLLMVTYCEDGRKVFESRDMGKTWTEAFGTLPGVWLKSGPELPEVSLRVDALITATIEGRKVM
LYTQKVRHFLEVDEPNALHLWVTDNNRTFHLGPFSVDCAENKTFANTLLYSDDALHLLQAKGDHESTAVS
LARLTEELNTINSVLSTWVQLDASFSESSIPTAGLVGFLSNTTSSGDTWIDGYRCMNATVTKAAKVENGF
KFTGPGSRATWPVNSRWDIKQYGFVDYNFTIVAMATIHQVPSESTPLLGASLRGNKRTKLIGLSYGAGGK
WETVYDGTKTVQGGTWEPGREYQVALMLQDGNKGFVYVDGVLVGNPAMLPTPEERWTEFSHFYFGGDEGD
SGSDATLTDVFLYNRPLSVGELKMIKEVEDKKEKGSGDSEDKKESGDSEDKKESGDSEDKKGSGDSEDKK
ESGDSEDKKESGDSEDKKGSGDGAFTPAVSNATTHTAEEETVNQSASGTFSITDSTEGDVSSDENGETTG
GADGQEEDIQPQDGEANAAALGLALKSSLGTSSQWDGSVAGTMRESRVLLPSLFLLLGLWGFAAL
Protective antigen
Following the intramuscular immunization of H-2(b) and H-2(d) mice with a plasmid DNA encoding an N-terminally truncated TSA-1 lacking or containing the C-terminal nonapeptide tandem repeats, the antibody level, CTL response, and protection against challenge with T. cruzi were assessed. In H-2(b) mice, antiparasite antibodies were induced only by immunization with the DNA construct encoding TSA-1 containing the C-terminal repeats. However, both DNA constructs were efficient in eliciting long-lasting CTL responses against the protective H-2Kb-restricted TSA-1515-522 epitope. In H-2(d) mice, inoculation with either of the two TSA-1-expressing vectors effectively generated antiparasite antibodies and primed CTLs that lysed T. cruzi-infected cells in an antigen-specific, MHC class I-restricted, and CD8(+)-T-cell-dependent manner. When TSA-1 DNA-vaccinated animals were challenged with T. cruzi, 14 of 22 (64%) H-2(b) and 16 of 18 (89%) H-2(d) mice survived the infection [Ref1352:Wizel et al., 1998].
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