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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Brenda Kischkel, Camila Boniche-Alfaro, Isabela de Godoy Menezes, Suelen Andreia Rossi, Claudia Blanes Angeli, Sandro Rogério de Almeida, Giuseppe Palmisano, Leila Lopes-Bezerra, Joshua D. Nosanchuk, Carlos Pelleschi Taborda
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	vaccine pan-fungal peptide dimorphic-fungi proteomic Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/2fd4aaf9f76b48d4a04e8d5b14f7f9c2
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:2fd4aaf9f76b48d4a04e8d5b14f7f9c2
record_format	dspace
spelling	oai:doaj.org-article:2fd4aaf9f76b48d4a04e8d5b14f7f9c22021-11-22T06:36:26ZImmunoproteomic and Immunopeptidomic Analyses of Histoplasma capsulatum Reveal Promiscuous and Conserved Epitopes Among Fungi With Vaccine Potential1664-322410.3389/fimmu.2021.764501https://doaj.org/article/2fd4aaf9f76b48d4a04e8d5b14f7f9c22021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.764501/fullhttps://doaj.org/toc/1664-3224As 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.Brenda KischkelCamila Boniche-AlfaroIsabela de Godoy MenezesSuelen Andreia RossiSuelen Andreia RossiClaudia Blanes AngeliSandro Rogério de AlmeidaGiuseppe PalmisanoLeila Lopes-BezerraJoshua D. NosanchukJoshua D. NosanchukCarlos Pelleschi TabordaCarlos Pelleschi TabordaFrontiers Media S.A.articlevaccinepan-fungalpeptidedimorphic-fungiproteomicImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	vaccine pan-fungal peptide dimorphic-fungi proteomic Immunologic diseases. Allergy RC581-607
spellingShingle	vaccine pan-fungal peptide dimorphic-fungi proteomic Immunologic diseases. Allergy RC581-607 Brenda Kischkel Camila Boniche-Alfaro Isabela de Godoy Menezes Suelen Andreia Rossi Suelen Andreia Rossi Claudia Blanes Angeli Sandro Rogério de Almeida Giuseppe Palmisano Leila Lopes-Bezerra Joshua D. Nosanchuk Joshua D. Nosanchuk Carlos Pelleschi Taborda Carlos Pelleschi Taborda Immunoproteomic and Immunopeptidomic Analyses of Histoplasma capsulatum Reveal Promiscuous and Conserved Epitopes Among Fungi With Vaccine Potential
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	article
author	Brenda Kischkel Camila Boniche-Alfaro Isabela de Godoy Menezes Suelen Andreia Rossi Suelen Andreia Rossi Claudia Blanes Angeli Sandro Rogério de Almeida Giuseppe Palmisano Leila Lopes-Bezerra Joshua D. Nosanchuk Joshua D. Nosanchuk Carlos Pelleschi Taborda Carlos Pelleschi Taborda
author_facet	Brenda Kischkel Camila Boniche-Alfaro Isabela de Godoy Menezes Suelen Andreia Rossi Suelen Andreia Rossi Claudia Blanes Angeli Sandro Rogério de Almeida Giuseppe Palmisano Leila Lopes-Bezerra Joshua D. Nosanchuk Joshua D. Nosanchuk Carlos Pelleschi Taborda Carlos Pelleschi Taborda
author_sort	Brenda Kischkel
title	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_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_sort	immunoproteomic and immunopeptidomic analyses of histoplasma capsulatum reveal promiscuous and conserved epitopes among fungi with vaccine potential
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/2fd4aaf9f76b48d4a04e8d5b14f7f9c2
work_keys_str_mv	AT brendakischkel immunoproteomicandimmunopeptidomicanalysesofhistoplasmacapsulatumrevealpromiscuousandconservedepitopesamongfungiwithvaccinepotential AT camilabonichealfaro immunoproteomicandimmunopeptidomicanalysesofhistoplasmacapsulatumrevealpromiscuousandconservedepitopesamongfungiwithvaccinepotential AT isabeladegodoymenezes immunoproteomicandimmunopeptidomicanalysesofhistoplasmacapsulatumrevealpromiscuousandconservedepitopesamongfungiwithvaccinepotential AT suelenandreiarossi immunoproteomicandimmunopeptidomicanalysesofhistoplasmacapsulatumrevealpromiscuousandconservedepitopesamongfungiwithvaccinepotential AT suelenandreiarossi immunoproteomicandimmunopeptidomicanalysesofhistoplasmacapsulatumrevealpromiscuousandconservedepitopesamongfungiwithvaccinepotential AT claudiablanesangeli immunoproteomicandimmunopeptidomicanalysesofhistoplasmacapsulatumrevealpromiscuousandconservedepitopesamongfungiwithvaccinepotential AT sandrorogeriodealmeida immunoproteomicandimmunopeptidomicanalysesofhistoplasmacapsulatumrevealpromiscuousandconservedepitopesamongfungiwithvaccinepotential AT giuseppepalmisano immunoproteomicandimmunopeptidomicanalysesofhistoplasmacapsulatumrevealpromiscuousandconservedepitopesamongfungiwithvaccinepotential AT leilalopesbezerra immunoproteomicandimmunopeptidomicanalysesofhistoplasmacapsulatumrevealpromiscuousandconservedepitopesamongfungiwithvaccinepotential AT joshuadnosanchuk immunoproteomicandimmunopeptidomicanalysesofhistoplasmacapsulatumrevealpromiscuousandconservedepitopesamongfungiwithvaccinepotential AT joshuadnosanchuk immunoproteomicandimmunopeptidomicanalysesofhistoplasmacapsulatumrevealpromiscuousandconservedepitopesamongfungiwithvaccinepotential AT carlospelleschitaborda immunoproteomicandimmunopeptidomicanalysesofhistoplasmacapsulatumrevealpromiscuousandconservedepitopesamongfungiwithvaccinepotential AT carlospelleschitaborda immunoproteomicandimmunopeptidomicanalysesofhistoplasmacapsulatumrevealpromiscuousandconservedepitopesamongfungiwithvaccinepotential
_version_	1718418092892094464

Immunoproteomic and Immunopeptidomic Analyses of Histoplasma capsulatum Reveal Promiscuous and Conserved Epitopes Among Fungi With Vaccine Potential

Ejemplares similares