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The History of Anti-Trypanosome Vaccine Development Shows That Highly Immunogenic and Exposed Pathogen-Derived Antigens Are Not Necessarily Good Target Candidates: Enolase and ISG75 as Examples

Salivarian trypanosomes comprise a group of extracellular anthroponotic and zoonotic parasites. The only sustainable method for global control of these infection is through vaccination of livestock animals. Despite multiple reports describing promising laboratory results, no single field-applicable...

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Autores principales: Magez, Stefan, Li, Zeng, Nguyen, Hang Thi Thu, Pinto Torres, Joar Esteban, Van Wielendaele, Pieter, Radwanska, Magdalena, Began, Jakub, Zoll, Sebastian, Sterckx, Yann G.-J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8400590/
https://www.ncbi.nlm.nih.gov/pubmed/34451514
http://dx.doi.org/10.3390/pathogens10081050
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author Magez, Stefan
Li, Zeng
Nguyen, Hang Thi Thu
Pinto Torres, Joar Esteban
Van Wielendaele, Pieter
Radwanska, Magdalena
Began, Jakub
Zoll, Sebastian
Sterckx, Yann G.-J.
author_facet Magez, Stefan
Li, Zeng
Nguyen, Hang Thi Thu
Pinto Torres, Joar Esteban
Van Wielendaele, Pieter
Radwanska, Magdalena
Began, Jakub
Zoll, Sebastian
Sterckx, Yann G.-J.
author_sort Magez, Stefan
collection PubMed
description Salivarian trypanosomes comprise a group of extracellular anthroponotic and zoonotic parasites. The only sustainable method for global control of these infection is through vaccination of livestock animals. Despite multiple reports describing promising laboratory results, no single field-applicable solution has been successful so far. Conventionally, vaccine research focusses mostly on exposed immunogenic antigens, or the structural molecular knowledge of surface exposed invariant immunogens. Unfortunately, extracellular parasites (or parasites with extracellular life stages) have devised efficient defense systems against host antibody attacks, so they can deal with the mammalian humoral immune response. In the case of trypanosomes, it appears that these mechanisms have been perfected, leading to vaccine failure in natural hosts. Here, we provide two examples of potential vaccine candidates that, despite being immunogenic and accessible to the immune system, failed to induce a functionally protective memory response. First, trypanosomal enolase was tested as a vaccine candidate, as it was recently characterized as a highly conserved enzyme that is readily recognized during infection by the host antibody response. Secondly, we re-addressed a vaccine approach towards the Invariant Surface Glycoprotein ISG75, and showed that despite being highly immunogenic, trypanosomes can avoid anti-ISG75 mediated parasitemia control.
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spelling pubmed-84005902021-08-29 The History of Anti-Trypanosome Vaccine Development Shows That Highly Immunogenic and Exposed Pathogen-Derived Antigens Are Not Necessarily Good Target Candidates: Enolase and ISG75 as Examples Magez, Stefan Li, Zeng Nguyen, Hang Thi Thu Pinto Torres, Joar Esteban Van Wielendaele, Pieter Radwanska, Magdalena Began, Jakub Zoll, Sebastian Sterckx, Yann G.-J. Pathogens Article Salivarian trypanosomes comprise a group of extracellular anthroponotic and zoonotic parasites. The only sustainable method for global control of these infection is through vaccination of livestock animals. Despite multiple reports describing promising laboratory results, no single field-applicable solution has been successful so far. Conventionally, vaccine research focusses mostly on exposed immunogenic antigens, or the structural molecular knowledge of surface exposed invariant immunogens. Unfortunately, extracellular parasites (or parasites with extracellular life stages) have devised efficient defense systems against host antibody attacks, so they can deal with the mammalian humoral immune response. In the case of trypanosomes, it appears that these mechanisms have been perfected, leading to vaccine failure in natural hosts. Here, we provide two examples of potential vaccine candidates that, despite being immunogenic and accessible to the immune system, failed to induce a functionally protective memory response. First, trypanosomal enolase was tested as a vaccine candidate, as it was recently characterized as a highly conserved enzyme that is readily recognized during infection by the host antibody response. Secondly, we re-addressed a vaccine approach towards the Invariant Surface Glycoprotein ISG75, and showed that despite being highly immunogenic, trypanosomes can avoid anti-ISG75 mediated parasitemia control. MDPI 2021-08-19 /pmc/articles/PMC8400590/ /pubmed/34451514 http://dx.doi.org/10.3390/pathogens10081050 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Magez, Stefan
Li, Zeng
Nguyen, Hang Thi Thu
Pinto Torres, Joar Esteban
Van Wielendaele, Pieter
Radwanska, Magdalena
Began, Jakub
Zoll, Sebastian
Sterckx, Yann G.-J.
The History of Anti-Trypanosome Vaccine Development Shows That Highly Immunogenic and Exposed Pathogen-Derived Antigens Are Not Necessarily Good Target Candidates: Enolase and ISG75 as Examples
title The History of Anti-Trypanosome Vaccine Development Shows That Highly Immunogenic and Exposed Pathogen-Derived Antigens Are Not Necessarily Good Target Candidates: Enolase and ISG75 as Examples
title_full The History of Anti-Trypanosome Vaccine Development Shows That Highly Immunogenic and Exposed Pathogen-Derived Antigens Are Not Necessarily Good Target Candidates: Enolase and ISG75 as Examples
title_fullStr The History of Anti-Trypanosome Vaccine Development Shows That Highly Immunogenic and Exposed Pathogen-Derived Antigens Are Not Necessarily Good Target Candidates: Enolase and ISG75 as Examples
title_full_unstemmed The History of Anti-Trypanosome Vaccine Development Shows That Highly Immunogenic and Exposed Pathogen-Derived Antigens Are Not Necessarily Good Target Candidates: Enolase and ISG75 as Examples
title_short The History of Anti-Trypanosome Vaccine Development Shows That Highly Immunogenic and Exposed Pathogen-Derived Antigens Are Not Necessarily Good Target Candidates: Enolase and ISG75 as Examples
title_sort history of anti-trypanosome vaccine development shows that highly immunogenic and exposed pathogen-derived antigens are not necessarily good target candidates: enolase and isg75 as examples
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8400590/
https://www.ncbi.nlm.nih.gov/pubmed/34451514
http://dx.doi.org/10.3390/pathogens10081050
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