Trypanosoma cruzi 80 kDa prolyl oligopeptidase (Tc80) as a novel immunogen for Chagas disease vaccine.
BACKGROUND:Chagas disease, also known as American Trypanosomiasis, is a chronic parasitic disease caused by the flagellated protozoan Trypanosoma cruzi that affects about 8 million people around the world where more than 25 million are at risk of contracting the infection. Despite of being endemic o...
Published in: | PLOS Neglected Tropical Diseases |
---|---|
Main Authors: | , , , , , , , , |
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
Public Library of Science (PLoS)
2018
|
Subjects: | |
Online Access: | https://doi.org/10.1371/journal.pntd.0006384 https://doaj.org/article/0d512db3082c43d19ad04f699b3f8d76 |
id |
ftdoajarticles:oai:doaj.org/article:0d512db3082c43d19ad04f699b3f8d76 |
---|---|
record_format |
openpolar |
spelling |
ftdoajarticles:oai:doaj.org/article:0d512db3082c43d19ad04f699b3f8d76 2023-05-15T15:11:43+02:00 Trypanosoma cruzi 80 kDa prolyl oligopeptidase (Tc80) as a novel immunogen for Chagas disease vaccine. Augusto E Bivona Andrés Sánchez Alberti Marina N Matos Natacha Cerny Alejandro C Cardoso Celina Morales Germán González Silvia I Cazorla Emilio L Malchiodi 2018-03-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0006384 https://doaj.org/article/0d512db3082c43d19ad04f699b3f8d76 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC5895069?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0006384 https://doaj.org/article/0d512db3082c43d19ad04f699b3f8d76 PLoS Neglected Tropical Diseases, Vol 12, Iss 3, p e0006384 (2018) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2018 ftdoajarticles https://doi.org/10.1371/journal.pntd.0006384 2022-12-31T02:16:11Z BACKGROUND:Chagas disease, also known as American Trypanosomiasis, is a chronic parasitic disease caused by the flagellated protozoan Trypanosoma cruzi that affects about 8 million people around the world where more than 25 million are at risk of contracting the infection. Despite of being endemic on 21 Latin-American countries, Chagas disease has become a global concern due to migratory movements. Unfortunately, available drugs for the treatment have several limitations and they are generally administered during the chronic phase of the infection, when its efficacy is considered controversial. Thus, prophylactic and/or therapeutic vaccines are emerging as interesting control alternatives. In this work, we proposed Trypanosoma cruzi 80 kDa prolyl oligopeptidase (Tc80) as a new antigen for vaccine development against Chagas disease. METHODOLOGY/PRINCIPAL FINDINGS:In a murine model, we analyzed the immune response triggered by different immunization protocols based on Tc80 and evaluated their ability to confer protection against a challenge with the parasite. Immunized mice developed Tc80-specific antibodies which were able to carry out different functions such as: enzymatic inhibition, neutralization of parasite infection and complement-mediated lysis of trypomastigotes. Furthermore, vaccinated mice elicited strong cell-mediated immunity. Spleen cells from immunized mice proliferated and secreted Th1 cytokines (IL-2, IFN-γ and TNF-α) upon re-stimulation with rTc80. Moreover, we found Tc80-specific polyfunctional CD4 T cells, and cytotoxic T lymphocyte activity against one Tc80 MHC-I peptide. Immunization protocols conferred protection against a T. cruzi lethal challenge. 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. CONCLUSIONS/SIGNIFICANCE:Considering that ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 12 3 e0006384 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Augusto E Bivona Andrés Sánchez Alberti Marina N Matos Natacha Cerny Alejandro C Cardoso Celina Morales Germán González Silvia I Cazorla Emilio L Malchiodi Trypanosoma cruzi 80 kDa prolyl oligopeptidase (Tc80) as a novel immunogen for Chagas disease vaccine. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
BACKGROUND:Chagas disease, also known as American Trypanosomiasis, is a chronic parasitic disease caused by the flagellated protozoan Trypanosoma cruzi that affects about 8 million people around the world where more than 25 million are at risk of contracting the infection. Despite of being endemic on 21 Latin-American countries, Chagas disease has become a global concern due to migratory movements. Unfortunately, available drugs for the treatment have several limitations and they are generally administered during the chronic phase of the infection, when its efficacy is considered controversial. Thus, prophylactic and/or therapeutic vaccines are emerging as interesting control alternatives. In this work, we proposed Trypanosoma cruzi 80 kDa prolyl oligopeptidase (Tc80) as a new antigen for vaccine development against Chagas disease. METHODOLOGY/PRINCIPAL FINDINGS:In a murine model, we analyzed the immune response triggered by different immunization protocols based on Tc80 and evaluated their ability to confer protection against a challenge with the parasite. Immunized mice developed Tc80-specific antibodies which were able to carry out different functions such as: enzymatic inhibition, neutralization of parasite infection and complement-mediated lysis of trypomastigotes. Furthermore, vaccinated mice elicited strong cell-mediated immunity. Spleen cells from immunized mice proliferated and secreted Th1 cytokines (IL-2, IFN-γ and TNF-α) upon re-stimulation with rTc80. Moreover, we found Tc80-specific polyfunctional CD4 T cells, and cytotoxic T lymphocyte activity against one Tc80 MHC-I peptide. Immunization protocols conferred protection against a T. cruzi lethal challenge. 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. CONCLUSIONS/SIGNIFICANCE:Considering that ... |
format |
Article in Journal/Newspaper |
author |
Augusto E Bivona Andrés Sánchez Alberti Marina N Matos Natacha Cerny Alejandro C Cardoso Celina Morales Germán González Silvia I Cazorla Emilio L Malchiodi |
author_facet |
Augusto E Bivona Andrés Sánchez Alberti Marina N Matos Natacha Cerny Alejandro C Cardoso Celina Morales Germán González Silvia I Cazorla Emilio L Malchiodi |
author_sort |
Augusto E Bivona |
title |
Trypanosoma cruzi 80 kDa prolyl oligopeptidase (Tc80) as a novel immunogen for Chagas disease vaccine. |
title_short |
Trypanosoma cruzi 80 kDa prolyl oligopeptidase (Tc80) as a novel immunogen for Chagas disease vaccine. |
title_full |
Trypanosoma cruzi 80 kDa prolyl oligopeptidase (Tc80) as a novel immunogen for Chagas disease vaccine. |
title_fullStr |
Trypanosoma cruzi 80 kDa prolyl oligopeptidase (Tc80) as a novel immunogen for Chagas disease vaccine. |
title_full_unstemmed |
Trypanosoma cruzi 80 kDa prolyl oligopeptidase (Tc80) as a novel immunogen for Chagas disease vaccine. |
title_sort |
trypanosoma cruzi 80 kda prolyl oligopeptidase (tc80) as a novel immunogen for chagas disease vaccine. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2018 |
url |
https://doi.org/10.1371/journal.pntd.0006384 https://doaj.org/article/0d512db3082c43d19ad04f699b3f8d76 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 12, Iss 3, p e0006384 (2018) |
op_relation |
http://europepmc.org/articles/PMC5895069?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0006384 https://doaj.org/article/0d512db3082c43d19ad04f699b3f8d76 |
op_doi |
https://doi.org/10.1371/journal.pntd.0006384 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
12 |
container_issue |
3 |
container_start_page |
e0006384 |
_version_ |
1766342528979697664 |