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Immunoproteomic and Immunopeptidomic Analyses of Histoplasma capsulatum Reveal Promiscuous and Conserved Epitopes Among Fungi With Vaccine Potential
As there are more than 6 million human deaths due to mycoses each year, there is an urgent need to develop fungal vaccines. Moreover, given the similarities among pathogenic fungi, it may be possible to create a multi-fungi vaccine. In this study, we combined immunoproteomic and immunopeptidomic met...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8645968/ https://www.ncbi.nlm.nih.gov/pubmed/34880863 http://dx.doi.org/10.3389/fimmu.2021.764501 |
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author | Kischkel, Brenda Boniche-Alfaro, Camila Menezes, Isabela de Godoy Rossi, Suelen Andreia Angeli, Claudia Blanes de Almeida, Sandro Rogério Palmisano, Giuseppe Lopes-Bezerra, Leila Nosanchuk, Joshua D. Taborda, Carlos Pelleschi |
author_facet | Kischkel, Brenda Boniche-Alfaro, Camila Menezes, Isabela de Godoy Rossi, Suelen Andreia Angeli, Claudia Blanes de Almeida, Sandro Rogério Palmisano, Giuseppe Lopes-Bezerra, Leila Nosanchuk, Joshua D. Taborda, Carlos Pelleschi |
author_sort | Kischkel, Brenda |
collection | PubMed |
description | As there are more than 6 million human deaths due to mycoses each year, there is an urgent need to develop fungal vaccines. Moreover, given the similarities among pathogenic fungi, it may be possible to create a multi-fungi vaccine. In this study, we combined immunoproteomic and immunopeptidomic methods, for which we have adapted a technique based on co-immunoprecipitation (Co-IP) that made it possible to map Histoplasma capsulatum epitopes for the first time in a natural context using murine dendritic cells (DCs) and macrophages (Mφ). Although polysaccharide epitopes exist, this research focused on mapping protein epitopes as these are more immunogenic. We used different algorithms to screen proteins and peptides identified by two-dimensional electrophoresis (2-D) and Co-IP. Seventeen proteins were revealed by 2-D gels, and 45 and 24 peptides from distinct proteins were presented by DCs and Mφ, respectively. We then determined which epitopes were restricted to MHC-I and II from humans and mice and showed high promiscuity, but lacked identity with human proteins. The 4 most promising peptides were synthesized, and the peptides with and without incorporation into glucan particles induced CD4+ and CD8+ T cell proliferation and produced a Th1 and Th17 response marked by the secretion of high levels of IFN-γ, IL-17 and IL-2. These epitopes were from heat shock protein 60, enolase, and the ATP-dependent molecular chaperone HSC82, and they each have a high degree of identity with proteins expressed by other medically important pathogenic fungi. Thus, the epitopes described in this study have the potential for use in the development of vaccines that could result in cross-protection among fungal species. |
format | Online Article Text |
id | pubmed-8645968 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-86459682021-12-07 Immunoproteomic and Immunopeptidomic Analyses of Histoplasma capsulatum Reveal Promiscuous and Conserved Epitopes Among Fungi With Vaccine Potential Kischkel, Brenda Boniche-Alfaro, Camila Menezes, Isabela de Godoy Rossi, Suelen Andreia Angeli, Claudia Blanes de Almeida, Sandro Rogério Palmisano, Giuseppe Lopes-Bezerra, Leila Nosanchuk, Joshua D. Taborda, Carlos Pelleschi Front Immunol Immunology As there are more than 6 million human deaths due to mycoses each year, there is an urgent need to develop fungal vaccines. Moreover, given the similarities among pathogenic fungi, it may be possible to create a multi-fungi vaccine. In this study, we combined immunoproteomic and immunopeptidomic methods, for which we have adapted a technique based on co-immunoprecipitation (Co-IP) that made it possible to map Histoplasma capsulatum epitopes for the first time in a natural context using murine dendritic cells (DCs) and macrophages (Mφ). Although polysaccharide epitopes exist, this research focused on mapping protein epitopes as these are more immunogenic. We used different algorithms to screen proteins and peptides identified by two-dimensional electrophoresis (2-D) and Co-IP. Seventeen proteins were revealed by 2-D gels, and 45 and 24 peptides from distinct proteins were presented by DCs and Mφ, respectively. We then determined which epitopes were restricted to MHC-I and II from humans and mice and showed high promiscuity, but lacked identity with human proteins. The 4 most promising peptides were synthesized, and the peptides with and without incorporation into glucan particles induced CD4+ and CD8+ T cell proliferation and produced a Th1 and Th17 response marked by the secretion of high levels of IFN-γ, IL-17 and IL-2. These epitopes were from heat shock protein 60, enolase, and the ATP-dependent molecular chaperone HSC82, and they each have a high degree of identity with proteins expressed by other medically important pathogenic fungi. Thus, the epitopes described in this study have the potential for use in the development of vaccines that could result in cross-protection among fungal species. Frontiers Media S.A. 2021-11-22 /pmc/articles/PMC8645968/ /pubmed/34880863 http://dx.doi.org/10.3389/fimmu.2021.764501 Text en Copyright © 2021 Kischkel, Boniche-Alfaro, Menezes, Rossi, Angeli, de Almeida, Palmisano, Lopes-Bezerra, Nosanchuk and Taborda https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Kischkel, Brenda Boniche-Alfaro, Camila Menezes, Isabela de Godoy Rossi, Suelen Andreia Angeli, Claudia Blanes de Almeida, Sandro Rogério Palmisano, Giuseppe Lopes-Bezerra, Leila Nosanchuk, Joshua D. Taborda, Carlos Pelleschi Immunoproteomic and Immunopeptidomic Analyses of Histoplasma capsulatum Reveal Promiscuous and Conserved Epitopes Among Fungi With Vaccine Potential |
title | Immunoproteomic and Immunopeptidomic Analyses of Histoplasma capsulatum Reveal Promiscuous and Conserved Epitopes Among Fungi With Vaccine Potential |
title_full | Immunoproteomic and Immunopeptidomic Analyses of Histoplasma capsulatum Reveal Promiscuous and Conserved Epitopes Among Fungi With Vaccine Potential |
title_fullStr | Immunoproteomic and Immunopeptidomic Analyses of Histoplasma capsulatum Reveal Promiscuous and Conserved Epitopes Among Fungi With Vaccine Potential |
title_full_unstemmed | Immunoproteomic and Immunopeptidomic Analyses of Histoplasma capsulatum Reveal Promiscuous and Conserved Epitopes Among Fungi With Vaccine Potential |
title_short | Immunoproteomic and Immunopeptidomic Analyses of Histoplasma capsulatum Reveal Promiscuous and Conserved Epitopes Among Fungi With Vaccine Potential |
title_sort | immunoproteomic and immunopeptidomic analyses of histoplasma capsulatum reveal promiscuous and conserved epitopes among fungi with vaccine potential |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8645968/ https://www.ncbi.nlm.nih.gov/pubmed/34880863 http://dx.doi.org/10.3389/fimmu.2021.764501 |
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