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Immune protection against Trypanosoma cruzi induced by TcVac4 in a canine model.

Aparicio-Burgos JE, Zepeda-Escobar JA, de Oca-Jimenez RM, Estrada-Franco JG, Barbabosa-Pliego A, Ochoa-García L, Alejandre-Aguilar R, Rivas N, Peñuelas-Rivas G, Val-Arreola M, Gupta S, Salazar-García F, Garg NJ, Vázquez-Chagoyán JC - PLoS Negl Trop Dis (2015)

Bottom Line: TcVac4 induced a strong IgG response (IgG2>IgG1) that was significantly expanded post-infection, and moved to a nearly balanced IgG2/IgG1 response in chronic phase.We conclude that TcVac4 induced immunity was beneficial in providing resistance to T. cruzi infection, evidenced by control of chronic pathology of the heart and preservation of cardiac function in dogs.Additionally, TcVac4 vaccination decreased the transmission of parasites from vaccinated/infected animals to triatomines.

View Article: PubMed Central - PubMed

Affiliation: Escuela Superior de Apan-Universidad Autónoma del Estado de Hidalgo, Apan Hidalgo, México.

ABSTRACT
Chagas disease, caused by Trypanosoma cruzi, is endemic in southern parts of the American continent. Herein, we have tested the protective efficacy of a DNA-prime/T. rangeli-boost (TcVac4) vaccine in a dog (Canis familiaris) model. Dogs were immunized with two-doses of DNA vaccine (pcDNA3.1 encoding TcG1, TcG2, and TcG4 antigens plus IL-12- and GM-CSF-encoding plasmids) followed by two doses of glutaraldehyde-inactivated T. rangeli epimastigotes (TrIE); and challenged with highly pathogenic T. cruzi (SylvioX10/4) isolate. Dogs given TrIE or empty pcDNA3.1 were used as controls. We monitored post-vaccination and post-challenge infection antibody response by an ELISA, parasitemia by blood analysis and xenodiagnosis, and heart function by electrocardiography. Post-mortem anatomic and pathologic evaluation of the heart was conducted. TcVac4 induced a strong IgG response (IgG2>IgG1) that was significantly expanded post-infection, and moved to a nearly balanced IgG2/IgG1 response in chronic phase. In comparison, dogs given TrIE or empty plasmid DNA only developed high IgG titers with IgG2 predominance in response to T. cruzi infection. Blood parasitemia, tissue parasite foci, parasite transmission to triatomines, electrocardiographic abnormalities were significantly lower in TcVac4-vaccinated dogs than was observed in dogs given TrIE or empty plasmid DNA only. Macroscopic and microscopic alterations, the hallmarks of chronic Chagas disease, were significantly decreased in the myocardium of TcVac4-vaccinated dogs. We conclude that TcVac4 induced immunity was beneficial in providing resistance to T. cruzi infection, evidenced by control of chronic pathology of the heart and preservation of cardiac function in dogs. Additionally, TcVac4 vaccination decreased the transmission of parasites from vaccinated/infected animals to triatomines.

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TcVac4-induced antibody response in dogs (± T. cruzi).Dogs were vaccinated with TcVac4 or TrIE only and infected with T. cruzi, as described in Materials and Methods. Shown are sera levels of T. cruzi-specific IgG (A), IgG1 (B), and IgG2 (C) antibody subtypes, determined by an ELISA. Dogs given pcDNA3.1/no infection and dogs given pcDNA3.1/T. cruzi were included as negative and positive controls, respectively. The serology time points are described as day -65 = basal response before immunization, day 0 representing antibody response after last immunization but before challenge infection, day 60 post challenge equivalent to acute infection phase, and day 365 post challenge equivalent to chronic disease phase. Each bar represents the absorbance mean value ± standard deviation. Within the same time point, statistical differences (p < 0.05) among groups are shown with different characters above the bars according to Tukey’s test.
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pntd.0003625.g001: TcVac4-induced antibody response in dogs (± T. cruzi).Dogs were vaccinated with TcVac4 or TrIE only and infected with T. cruzi, as described in Materials and Methods. Shown are sera levels of T. cruzi-specific IgG (A), IgG1 (B), and IgG2 (C) antibody subtypes, determined by an ELISA. Dogs given pcDNA3.1/no infection and dogs given pcDNA3.1/T. cruzi were included as negative and positive controls, respectively. The serology time points are described as day -65 = basal response before immunization, day 0 representing antibody response after last immunization but before challenge infection, day 60 post challenge equivalent to acute infection phase, and day 365 post challenge equivalent to chronic disease phase. Each bar represents the absorbance mean value ± standard deviation. Within the same time point, statistical differences (p < 0.05) among groups are shown with different characters above the bars according to Tukey’s test.

Mentions: Sera levels of T. cruzi-specific antibodies were determined by an ELISA test. All dogs were seronegative before vaccination was initiated. T. cruzi-specific antibody response (IgGs, 1:100-dilution) was detectable after first vaccine dose, and gradually increased with subsequent doses. The antibody response examined after last vaccine dose is shown in Fig 1. TcVac4/Tc dogs exhibited 2.2–4.9-fold higher level of T. cruzi-specific IgGs as compared to that noted in TrIE/Tc dogs (Fig 1A, p<0.05). Likewise, TcVac4/Tc dogs exhibited >3-fold increase in IgG1 and IgG2 levels (IgG2/IgG1 ratio: 2.23) when compared to that noted in sera of TrIE/Tc dogs (Fig 1B and 1C, p<0.05).


Immune protection against Trypanosoma cruzi induced by TcVac4 in a canine model.

Aparicio-Burgos JE, Zepeda-Escobar JA, de Oca-Jimenez RM, Estrada-Franco JG, Barbabosa-Pliego A, Ochoa-García L, Alejandre-Aguilar R, Rivas N, Peñuelas-Rivas G, Val-Arreola M, Gupta S, Salazar-García F, Garg NJ, Vázquez-Chagoyán JC - PLoS Negl Trop Dis (2015)

TcVac4-induced antibody response in dogs (± T. cruzi).Dogs were vaccinated with TcVac4 or TrIE only and infected with T. cruzi, as described in Materials and Methods. Shown are sera levels of T. cruzi-specific IgG (A), IgG1 (B), and IgG2 (C) antibody subtypes, determined by an ELISA. Dogs given pcDNA3.1/no infection and dogs given pcDNA3.1/T. cruzi were included as negative and positive controls, respectively. The serology time points are described as day -65 = basal response before immunization, day 0 representing antibody response after last immunization but before challenge infection, day 60 post challenge equivalent to acute infection phase, and day 365 post challenge equivalent to chronic disease phase. Each bar represents the absorbance mean value ± standard deviation. Within the same time point, statistical differences (p < 0.05) among groups are shown with different characters above the bars according to Tukey’s test.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4390229&req=5

pntd.0003625.g001: TcVac4-induced antibody response in dogs (± T. cruzi).Dogs were vaccinated with TcVac4 or TrIE only and infected with T. cruzi, as described in Materials and Methods. Shown are sera levels of T. cruzi-specific IgG (A), IgG1 (B), and IgG2 (C) antibody subtypes, determined by an ELISA. Dogs given pcDNA3.1/no infection and dogs given pcDNA3.1/T. cruzi were included as negative and positive controls, respectively. The serology time points are described as day -65 = basal response before immunization, day 0 representing antibody response after last immunization but before challenge infection, day 60 post challenge equivalent to acute infection phase, and day 365 post challenge equivalent to chronic disease phase. Each bar represents the absorbance mean value ± standard deviation. Within the same time point, statistical differences (p < 0.05) among groups are shown with different characters above the bars according to Tukey’s test.
Mentions: Sera levels of T. cruzi-specific antibodies were determined by an ELISA test. All dogs were seronegative before vaccination was initiated. T. cruzi-specific antibody response (IgGs, 1:100-dilution) was detectable after first vaccine dose, and gradually increased with subsequent doses. The antibody response examined after last vaccine dose is shown in Fig 1. TcVac4/Tc dogs exhibited 2.2–4.9-fold higher level of T. cruzi-specific IgGs as compared to that noted in TrIE/Tc dogs (Fig 1A, p<0.05). Likewise, TcVac4/Tc dogs exhibited >3-fold increase in IgG1 and IgG2 levels (IgG2/IgG1 ratio: 2.23) when compared to that noted in sera of TrIE/Tc dogs (Fig 1B and 1C, p<0.05).

Bottom Line: TcVac4 induced a strong IgG response (IgG2>IgG1) that was significantly expanded post-infection, and moved to a nearly balanced IgG2/IgG1 response in chronic phase.We conclude that TcVac4 induced immunity was beneficial in providing resistance to T. cruzi infection, evidenced by control of chronic pathology of the heart and preservation of cardiac function in dogs.Additionally, TcVac4 vaccination decreased the transmission of parasites from vaccinated/infected animals to triatomines.

View Article: PubMed Central - PubMed

Affiliation: Escuela Superior de Apan-Universidad Autónoma del Estado de Hidalgo, Apan Hidalgo, México.

ABSTRACT
Chagas disease, caused by Trypanosoma cruzi, is endemic in southern parts of the American continent. Herein, we have tested the protective efficacy of a DNA-prime/T. rangeli-boost (TcVac4) vaccine in a dog (Canis familiaris) model. Dogs were immunized with two-doses of DNA vaccine (pcDNA3.1 encoding TcG1, TcG2, and TcG4 antigens plus IL-12- and GM-CSF-encoding plasmids) followed by two doses of glutaraldehyde-inactivated T. rangeli epimastigotes (TrIE); and challenged with highly pathogenic T. cruzi (SylvioX10/4) isolate. Dogs given TrIE or empty pcDNA3.1 were used as controls. We monitored post-vaccination and post-challenge infection antibody response by an ELISA, parasitemia by blood analysis and xenodiagnosis, and heart function by electrocardiography. Post-mortem anatomic and pathologic evaluation of the heart was conducted. TcVac4 induced a strong IgG response (IgG2>IgG1) that was significantly expanded post-infection, and moved to a nearly balanced IgG2/IgG1 response in chronic phase. In comparison, dogs given TrIE or empty plasmid DNA only developed high IgG titers with IgG2 predominance in response to T. cruzi infection. Blood parasitemia, tissue parasite foci, parasite transmission to triatomines, electrocardiographic abnormalities were significantly lower in TcVac4-vaccinated dogs than was observed in dogs given TrIE or empty plasmid DNA only. Macroscopic and microscopic alterations, the hallmarks of chronic Chagas disease, were significantly decreased in the myocardium of TcVac4-vaccinated dogs. We conclude that TcVac4 induced immunity was beneficial in providing resistance to T. cruzi infection, evidenced by control of chronic pathology of the heart and preservation of cardiac function in dogs. Additionally, TcVac4 vaccination decreased the transmission of parasites from vaccinated/infected animals to triatomines.

Show MeSH
Related in: MedlinePlus