Limits...
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.

Show MeSH

Related in: MedlinePlus

Blood parasitemia control in dogs immunized with TcVac4.Dogs were immunized with TcVac4 or TrIE, and infected with T. cruzi as in Fig 1. Blood samples were evaluated for parasitemia by light microscopy at alternate days post-infection. Shown are data from day 16 to 46 after challenge infection, presented as mean values (n = 6/group). Different letters above lines show statistical differences (p< 0.05) among treatments within the same day of sampling according to Tukey’s test.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4390229&req=5

pntd.0003625.g002: Blood parasitemia control in dogs immunized with TcVac4.Dogs were immunized with TcVac4 or TrIE, and infected with T. cruzi as in Fig 1. Blood samples were evaluated for parasitemia by light microscopy at alternate days post-infection. Shown are data from day 16 to 46 after challenge infection, presented as mean values (n = 6/group). Different letters above lines show statistical differences (p< 0.05) among treatments within the same day of sampling according to Tukey’s test.

Mentions: Parasitemia was detected in all experimentally infected dogs. In general, pre-patent period lasted until 16 days pi and peak parasitemia was reached between days 32 and 37 pi in all infected dogs (Fig 2). The TcVac4/Tc dogs exhibited 4-fold lower level of peak parasitemia than was noted in TrIE/Tc or pcDNA3.1/Tc dogs. Further, in TcVac4/Tc dogs, parasitemia became undetectable at day 40 pi that was four days earlier than was noted in animals from other infected groups (Fig 2).


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)

Blood parasitemia control in dogs immunized with TcVac4.Dogs were immunized with TcVac4 or TrIE, and infected with T. cruzi as in Fig 1. Blood samples were evaluated for parasitemia by light microscopy at alternate days post-infection. Shown are data from day 16 to 46 after challenge infection, presented as mean values (n = 6/group). Different letters above lines show statistical differences (p< 0.05) among treatments within the same day of sampling according to Tukey’s test.
© Copyright Policy
Related In: Results  -  Collection

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

pntd.0003625.g002: Blood parasitemia control in dogs immunized with TcVac4.Dogs were immunized with TcVac4 or TrIE, and infected with T. cruzi as in Fig 1. Blood samples were evaluated for parasitemia by light microscopy at alternate days post-infection. Shown are data from day 16 to 46 after challenge infection, presented as mean values (n = 6/group). Different letters above lines show statistical differences (p< 0.05) among treatments within the same day of sampling according to Tukey’s test.
Mentions: Parasitemia was detected in all experimentally infected dogs. In general, pre-patent period lasted until 16 days pi and peak parasitemia was reached between days 32 and 37 pi in all infected dogs (Fig 2). The TcVac4/Tc dogs exhibited 4-fold lower level of peak parasitemia than was noted in TrIE/Tc or pcDNA3.1/Tc dogs. Further, in TcVac4/Tc dogs, parasitemia became undetectable at day 40 pi that was four days earlier than was noted in animals from other infected groups (Fig 2).

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