Location and expression kinetics of Tc24 in different life stages of Trypanosoma cruzi.
Tc24-C4, a modified recombinant flagellar calcium-binding protein of Trypanosoma cruzi, is under development as a therapeutic subunit vaccine candidate to prevent or delay progression of chronic Chagasic cardiomyopathy. When combined with Toll-like receptor agonists, Tc24-C4 immunization reduces par...
Published in: | PLOS Neglected Tropical Diseases |
---|---|
Main Authors: | , , , , , , , , |
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
Public Library of Science (PLoS)
2021
|
Subjects: | |
Online Access: | https://doi.org/10.1371/journal.pntd.0009689 https://doaj.org/article/58d767582fa0422791889d37f049cef3 |
id |
ftdoajarticles:oai:doaj.org/article:58d767582fa0422791889d37f049cef3 |
---|---|
record_format |
openpolar |
spelling |
ftdoajarticles:oai:doaj.org/article:58d767582fa0422791889d37f049cef3 2023-05-15T15:09:48+02:00 Location and expression kinetics of Tc24 in different life stages of Trypanosoma cruzi. Leroy Versteeg Rakesh Adhikari Cristina Poveda Maria Jose Villar-Mondragon Kathryn M Jones Peter J Hotez Maria Elena Bottazzi Edwin Tijhaar Jeroen Pollet 2021-09-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0009689 https://doaj.org/article/58d767582fa0422791889d37f049cef3 EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0009689 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0009689 https://doaj.org/article/58d767582fa0422791889d37f049cef3 PLoS Neglected Tropical Diseases, Vol 15, Iss 9, p e0009689 (2021) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2021 ftdoajarticles https://doi.org/10.1371/journal.pntd.0009689 2022-12-31T11:27:26Z Tc24-C4, a modified recombinant flagellar calcium-binding protein of Trypanosoma cruzi, is under development as a therapeutic subunit vaccine candidate to prevent or delay progression of chronic Chagasic cardiomyopathy. When combined with Toll-like receptor agonists, Tc24-C4 immunization reduces parasitemia, parasites in cardiac tissue, and cardiac fibrosis and inflammation in animal models. To support further research on the vaccine candidate and its mechanism of action, murine monoclonal antibodies (mAbs) against Tc24-C4 were generated. Here, we report new findings made with mAb Tc24-C4/884 that detects Tc24-WT and Tc24-C4, as well as native Tc24 in T. cruzi on ELISA, western blots, and different imaging techniques. Surprisingly, detection of Tc24 by Tc24-C/884 in fixed T. cruzi trypomastigotes required permeabilization of the parasite, revealing that Tc24 is not exposed on the surface of T. cruzi, making a direct role of antibodies in the induced protection after Tc24-C4 immunization less likely. We further observed that after immunostaining T. cruzi-infected cells with mAb Tc24-C4/884, the expression of Tc24 decreases significantly when T. cruzi trypomastigotes enter host cells and transform into amastigotes. However, Tc24 is then upregulated in association with parasite flagellar growth linked to re-transformation into the trypomastigote form, prior to host cellular escape. These observations are discussed in the context of potential mechanisms of vaccine immunity. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 15 9 e0009689 |
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 Leroy Versteeg Rakesh Adhikari Cristina Poveda Maria Jose Villar-Mondragon Kathryn M Jones Peter J Hotez Maria Elena Bottazzi Edwin Tijhaar Jeroen Pollet Location and expression kinetics of Tc24 in different life stages of Trypanosoma cruzi. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Tc24-C4, a modified recombinant flagellar calcium-binding protein of Trypanosoma cruzi, is under development as a therapeutic subunit vaccine candidate to prevent or delay progression of chronic Chagasic cardiomyopathy. When combined with Toll-like receptor agonists, Tc24-C4 immunization reduces parasitemia, parasites in cardiac tissue, and cardiac fibrosis and inflammation in animal models. To support further research on the vaccine candidate and its mechanism of action, murine monoclonal antibodies (mAbs) against Tc24-C4 were generated. Here, we report new findings made with mAb Tc24-C4/884 that detects Tc24-WT and Tc24-C4, as well as native Tc24 in T. cruzi on ELISA, western blots, and different imaging techniques. Surprisingly, detection of Tc24 by Tc24-C/884 in fixed T. cruzi trypomastigotes required permeabilization of the parasite, revealing that Tc24 is not exposed on the surface of T. cruzi, making a direct role of antibodies in the induced protection after Tc24-C4 immunization less likely. We further observed that after immunostaining T. cruzi-infected cells with mAb Tc24-C4/884, the expression of Tc24 decreases significantly when T. cruzi trypomastigotes enter host cells and transform into amastigotes. However, Tc24 is then upregulated in association with parasite flagellar growth linked to re-transformation into the trypomastigote form, prior to host cellular escape. These observations are discussed in the context of potential mechanisms of vaccine immunity. |
format |
Article in Journal/Newspaper |
author |
Leroy Versteeg Rakesh Adhikari Cristina Poveda Maria Jose Villar-Mondragon Kathryn M Jones Peter J Hotez Maria Elena Bottazzi Edwin Tijhaar Jeroen Pollet |
author_facet |
Leroy Versteeg Rakesh Adhikari Cristina Poveda Maria Jose Villar-Mondragon Kathryn M Jones Peter J Hotez Maria Elena Bottazzi Edwin Tijhaar Jeroen Pollet |
author_sort |
Leroy Versteeg |
title |
Location and expression kinetics of Tc24 in different life stages of Trypanosoma cruzi. |
title_short |
Location and expression kinetics of Tc24 in different life stages of Trypanosoma cruzi. |
title_full |
Location and expression kinetics of Tc24 in different life stages of Trypanosoma cruzi. |
title_fullStr |
Location and expression kinetics of Tc24 in different life stages of Trypanosoma cruzi. |
title_full_unstemmed |
Location and expression kinetics of Tc24 in different life stages of Trypanosoma cruzi. |
title_sort |
location and expression kinetics of tc24 in different life stages of trypanosoma cruzi. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2021 |
url |
https://doi.org/10.1371/journal.pntd.0009689 https://doaj.org/article/58d767582fa0422791889d37f049cef3 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 15, Iss 9, p e0009689 (2021) |
op_relation |
https://doi.org/10.1371/journal.pntd.0009689 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0009689 https://doaj.org/article/58d767582fa0422791889d37f049cef3 |
op_doi |
https://doi.org/10.1371/journal.pntd.0009689 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
15 |
container_issue |
9 |
container_start_page |
e0009689 |
_version_ |
1766340921112133632 |