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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
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.
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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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