Identifying molecularly defined antigens for a Histoplasma capsulatum-specific interferon gamma release assay [Identificación de antígenos definidos molecularmente para un ensayo de liberación de interferón-gamma específico para Histoplasma capsulatum]

Background: In a previous work we showed the feasibility of an interferon gamma release assay (IGRA) for detecting latent infection by Histoplasma capsulatum. While in that proof-of-concept study we used crude fungal extracts as antigens, the newest IGRAs developed for other infections are based on...

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Tipo de recurso:
Fecha de publicación:
2019
Institución:
Universidad de Medellín
Repositorio:
Repositorio UDEM
Idioma:
eng
spa
OAI Identifier:
oai:repository.udem.edu.co:11407/5812
Acceso en línea:
http://hdl.handle.net/11407/5812
Palabra clave:
Histoplasma capsulatum
IGRA
Immunogenic proteins
Molecularly defined antigens
T-cell epitopes
alcohol dehydrogenase
ankyrin repeat protein
beta lactamase
chaperonin 60
DUF636 domain containing protein
epitope
fungus antigen
M antigen
proteoglycan
synthetic peptide
unclassified drug
allele
amino acid sequence
antigen detection
antigenic variation
Article
controlled study
Histoplasma capsulatum
human
immunogenicity
interferon gamma release assay
nonhuman
orthology
pathogenicity
protein analysis
sensitivity and specificity
volunteer
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http://purl.org/coar/access_right/c_16ec
id REPOUDEM2_86638152030a9c85be20c66168a8a18d
oai_identifier_str oai:repository.udem.edu.co:11407/5812
network_acronym_str REPOUDEM2
network_name_str Repositorio UDEM
repository_id_str
dc.title.none.fl_str_mv Identifying molecularly defined antigens for a Histoplasma capsulatum-specific interferon gamma release assay [Identificación de antígenos definidos molecularmente para un ensayo de liberación de interferón-gamma específico para Histoplasma capsulatum]
title Identifying molecularly defined antigens for a Histoplasma capsulatum-specific interferon gamma release assay [Identificación de antígenos definidos molecularmente para un ensayo de liberación de interferón-gamma específico para Histoplasma capsulatum]
spellingShingle Identifying molecularly defined antigens for a Histoplasma capsulatum-specific interferon gamma release assay [Identificación de antígenos definidos molecularmente para un ensayo de liberación de interferón-gamma específico para Histoplasma capsulatum]
Histoplasma capsulatum
IGRA
Immunogenic proteins
Molecularly defined antigens
T-cell epitopes
alcohol dehydrogenase
ankyrin repeat protein
beta lactamase
chaperonin 60
DUF636 domain containing protein
epitope
fungus antigen
M antigen
proteoglycan
synthetic peptide
unclassified drug
allele
amino acid sequence
antigen detection
antigenic variation
Article
controlled study
Histoplasma capsulatum
human
immunogenicity
interferon gamma release assay
nonhuman
orthology
pathogenicity
protein analysis
sensitivity and specificity
volunteer
title_short Identifying molecularly defined antigens for a Histoplasma capsulatum-specific interferon gamma release assay [Identificación de antígenos definidos molecularmente para un ensayo de liberación de interferón-gamma específico para Histoplasma capsulatum]
title_full Identifying molecularly defined antigens for a Histoplasma capsulatum-specific interferon gamma release assay [Identificación de antígenos definidos molecularmente para un ensayo de liberación de interferón-gamma específico para Histoplasma capsulatum]
title_fullStr Identifying molecularly defined antigens for a Histoplasma capsulatum-specific interferon gamma release assay [Identificación de antígenos definidos molecularmente para un ensayo de liberación de interferón-gamma específico para Histoplasma capsulatum]
title_full_unstemmed Identifying molecularly defined antigens for a Histoplasma capsulatum-specific interferon gamma release assay [Identificación de antígenos definidos molecularmente para un ensayo de liberación de interferón-gamma específico para Histoplasma capsulatum]
title_sort Identifying molecularly defined antigens for a Histoplasma capsulatum-specific interferon gamma release assay [Identificación de antígenos definidos molecularmente para un ensayo de liberación de interferón-gamma específico para Histoplasma capsulatum]
dc.subject.none.fl_str_mv Histoplasma capsulatum
IGRA
Immunogenic proteins
Molecularly defined antigens
T-cell epitopes
alcohol dehydrogenase
ankyrin repeat protein
beta lactamase
chaperonin 60
DUF636 domain containing protein
epitope
fungus antigen
M antigen
proteoglycan
synthetic peptide
unclassified drug
allele
amino acid sequence
antigen detection
antigenic variation
Article
controlled study
Histoplasma capsulatum
human
immunogenicity
interferon gamma release assay
nonhuman
orthology
pathogenicity
protein analysis
sensitivity and specificity
volunteer
topic Histoplasma capsulatum
IGRA
Immunogenic proteins
Molecularly defined antigens
T-cell epitopes
alcohol dehydrogenase
ankyrin repeat protein
beta lactamase
chaperonin 60
DUF636 domain containing protein
epitope
fungus antigen
M antigen
proteoglycan
synthetic peptide
unclassified drug
allele
amino acid sequence
antigen detection
antigenic variation
Article
controlled study
Histoplasma capsulatum
human
immunogenicity
interferon gamma release assay
nonhuman
orthology
pathogenicity
protein analysis
sensitivity and specificity
volunteer
description Background: In a previous work we showed the feasibility of an interferon gamma release assay (IGRA) for detecting latent infection by Histoplasma capsulatum. While in that proof-of-concept study we used crude fungal extracts as antigens, the newest IGRAs developed for other infections are based on molecularly defined antigens, mostly on mixtures of immunogenic peptides. Aims: To identify proteins in H. capsulatum that might serve as molecularly defined antigens for an IGRA test. Methods: We surveyed the literature looking for known H. capsulatum-immunogenic proteins and assayed two of them as antigens in an IGRA test, in a study that involved 80 volunteers. Furthermore, we used several bioinformatics tools to identify specific H. capsulatum proteins and to analyze possible strategies for the design of H. capsulatum-specific immunogenic peptides. Results: Seven H. capsulatum-immunogenic proteins were retrieved from the literature. IGRA tests using either the heat shock protein 60 or the M antigen showed high sensitivities but low specificities, most likely due to the high sequence similarity with the corresponding orthologs in other pathogenic microorganisms. We identified around 2000 H. capsulatum-specific proteins, most of which remain unannotated. Class II T-cell epitope predictions for a small number of these proteins showed a great variability among different alleles, prompting for a brute force approach for peptide design. Conclusions: The H. capsulatum genome encodes a large number of distinctive proteins, which represent a valuable source of potential specific antigens for an IGRA test. Among them, the Cfp4 protein stands out as a very attractive candidate. © 2019 Asociación Española de Micología
publishDate 2019
dc.date.accessioned.none.fl_str_mv 2020-04-29T14:54:07Z
dc.date.available.none.fl_str_mv 2020-04-29T14:54:07Z
dc.date.none.fl_str_mv 2019
dc.type.eng.fl_str_mv Article
dc.type.coarversion.fl_str_mv http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.coar.fl_str_mv http://purl.org/coar/resource_type/c_6501
http://purl.org/coar/resource_type/c_2df8fbb1
dc.type.driver.none.fl_str_mv info:eu-repo/semantics/article
dc.identifier.issn.none.fl_str_mv 11301406
dc.identifier.uri.none.fl_str_mv http://hdl.handle.net/11407/5812
dc.identifier.doi.none.fl_str_mv 10.1016/j.riam.2019.06.002
identifier_str_mv 11301406
10.1016/j.riam.2019.06.002
url http://hdl.handle.net/11407/5812
dc.language.iso.none.fl_str_mv eng
spa
language eng
spa
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dc.relation.citationvolume.none.fl_str_mv 36
dc.relation.citationissue.none.fl_str_mv 4
dc.relation.citationstartpage.none.fl_str_mv 186
dc.relation.citationendpage.none.fl_str_mv 191
dc.relation.references.none.fl_str_mv Aagaard, C., Brock, I., Olsen, A., Ottenhoff, T.H.M., Weldingh, K., Andersen, P., Mapping immune reactivity toward Rv2653 and Rv2654: two novel low-molecular-mass antigens found specifically in the Mycobacterium tuberculosis complex (2004) J Infect Dis, 189, pp. 812-819
Adenis, A., Aznar, C., Couppié, P., Histoplasmosis in HIV-infected patients: a review of new developments and remaining gaps (2014) Curr Trop Med Rep, 1, pp. 119-128
Albuquerque, P.C., Nakayasu, E.S., Rodrigues, M.L., Frases, S., Casadevall, A., Zancope-Oliveira, R.M., Vesicular transport in Histoplasma capsulatum: an effective mechanism for trans-cell wall transfer of proteins and lipids in ascomycetes (2008) Cell Microbiol, 10, pp. 1695-1710
Allendoerfer, R., Deepe, G.S., Intrapulmonary response to Histoplasma capsulatum in gamma interferon knockout mice (1997) Infect Immun, 65, pp. 2564-2569
Barcellini, L., Borroni, E., Brown, J., Brunetti, E., Codecasa, L., Cugnata, F., First independent evaluation of QuantiFERON-TB Plus performance (2016) Eur Respir J, 47, pp. 1587-1590
Bendtsen, J.D., Jensen, L.J., Blom, N., Von Heijne, G., Brunak, S., Feature-based prediction of non-classical and leaderless protein secretion (2004) Protein Eng Des Sel, 17, pp. 349-356
Chapey, E., Wallon, M., Debize, G., Rabilloud, M., Peyron, F., Diagnosis of congenital toxoplasmosis by using a whole-blood gamma interferon release assay (2010) J Clin Microbiol, 48, pp. 41-45
Dammermann, W., Bentzien, F., Stiel, E.M., Kühne, C., Ullrich, S., zur Wiesch, J.S., Development of a novel IGRA assay to test T cell responsiveness to HBV antigens in whole blood of chronic hepatitis B patients (2015) J Transl Med, 13, p. 157
Deepe, G.S., Histoplasma capsulatum (histoplasmosis) (2014) Mandell, Douglas, and Bennett's principles and practice of infectious diseases, pp. 2949-2962
Dominguez, M.R., Silveira, E.L., de Vasconcelos, J.R., de Alencar, B.C., Machado, A.V., Bruna-Romero, O., Subdominant/cryptic CD8 T cell epitopes contribute to resistance against experimental infection with a human protozoan parasite (2011) PLoS ONE, 6, pp. 1-12
Emanuelsson, O., Nielsen, H., Brunak, S., von Heijne, G., Predicting subcellular localization of proteins based on their N-terminal amino acid sequence (2000) J Mol Biol, 300, pp. 1005-1016
Gidwani, K., Jones, S., Kumar, R., Boelaert, M., Sundar, S., Interferon-Gamma release assay (modified quantiFERON) as a potential marker of infection for Leishmania donovani, a proof of concept study (2011) PLoS Negl Trop Dis, 5, p. e1042
Giulieri, S., Manuel, O., QuantiFERON®-CMV assay for the assessment of cytomegalovirus cell-mediated immunity (2011) Expert Rev Mol Diagn, 11, pp. 17-25
Guimarães, A.J., Hamilton, A.J., de M Guedes, H.L., Nosanchuk, J.D., Zancopé-Oliveira, R.M., Biological function and molecular mapping of M antigen in yeast phase of Histoplasma capsulatum (2008) PLoS ONE, 3, p. e3449
Guimarães, A.J., Frases, S., Gomez, F.J., Zancopé-Oliveira, R.M., Nosanchuk, J.D., Monoclonal antibodies to heat shock protein 60 alter the pathogenesis of Histoplasma capsulatum (2009) Infect Immun, 77, pp. 1357-1367
Hober, D., Benyoucef, S., Chehadeh, W., Hober, D., Benyoucef, S., Chehadeh, W., Ex vivo interferon-gamma response to human immunodeficiency virus-1 derived peptides in human immunodeficiency virus-1 infected patients (2000) Scand J Immunol, 51, pp. 429-433
Holbrook, E.D., Kemski, M.M., Richer, S.M., Wheat, L.J., Rappleye, C.A., Glycosylation and immunoreactivity of the Histoplasma capsulatum Cfp4 yeast-phase exoantigen (2014) Infect Immun, 82, pp. 4414-4425
Horwath, M.C., Fecher, R.A., Deepe, G.S., Histoplasma capsulatum, lung infection and immunity (2015) Future Microbiol, 10, pp. 967-975
Jensen, K.K., Andreatta, M., Marcatili, P., Buus, S., Greenbaum, J.A., Yan, Z., Improved methods for predicting peptide binding affinity to MHC class II molecules (2018) Immunology, 154, pp. 394-406
Krogh, A., Larsson, B., Von Heijne, G., Sonnhammer, E.L.L., Predicting transmembrane protein topology with a hidden Markov model: application to complete genomes (2001) J Mol Biol, 305, pp. 567-580
Li, L., Stoeckert, C.J., Roos, D.S., OrthoMCL: identification of ortholog groups for eukaryotic genomes (2003) Genome Res, 13, pp. 2178-2189
Mazurek, G.H., Villarino, M.E., Guidelines for using the QuantiFERON-TB test for diagnosing latent Mycobacterium tuberculosis infection. Centers for Disease Control and Prevention (2003) MMWR Recomm Rep, 52, pp. 15-18
Nel, J.S., Bartelt, L.A., van Duin, D., Lachiewicz, A.M., Endemic mycoses in solid organ transplant recipients (2018) Infect Dis Clin N Am, 32, pp. 667-685
Rubio-Carrasquilla, M., Santa, C.D., Rendón, J.P., Botero-Garcés, J., Moreno, E., Cano, L.E., An interferon gamma release assay specific for Histoplasma capsulatum to detect asymptomatic infected individuals: a proof of concept study (2019) Med Mycol, 57, pp. 724-732
Sifuentes-Osornio, J., Corzo-León, D.E., Ponce-De-León, L.A., Epidemiology of invasive fungal infections in Latin America (2012) Curr Fungal Infect Rep, 6, pp. 23-34
Smith, J.G., Liu, X., Kaufhold, R.M., Clair, J., Caulfield, M.J., Development and validation of a gamma interferon ELISPOT assay for quantitation of cellular immune responses to varicella-zoster virus (2001) Clin Diagn Lab Immunol, 8, pp. 871-879
Turgay, N., Balcioglu, I.C., Toz, S.O., Ozbel, Y., Jones, S.L., Short report: Quantiferon-Leishmania as an epidemiological tool for evaluating the exposure to Leishmania infection (2010) Am J Trop Med Hyg, 83, pp. 822-824
Vergidis, P., Avery, R.K., Wheat, L.J., Dotson, J.L., Assi, M.A., Antoun, S.A., Histoplasmosis complicating tumor necrosis factor-? blocker therapy: a retrospective analysis of 98 cases (2015) Clin Infect Dis, 61, pp. 409-417
Weir, R.E., Morgan, A.R., Britton, W.J., Butlin, C.R., Dockrell, H.M., Development of a whole blood assay to measure T cell responses to leprosy: a new tool for immuno-epidemiological field studies of leprosy immunity (1994) J Immunol Methods, 176, pp. 93-101
dc.rights.coar.fl_str_mv http://purl.org/coar/access_right/c_16ec
rights_invalid_str_mv http://purl.org/coar/access_right/c_16ec
dc.publisher.none.fl_str_mv Asociacion Espanola de Micologia
dc.publisher.program.none.fl_str_mv Facultad de Ciencias Básicas
dc.publisher.faculty.none.fl_str_mv Facultad de Ciencias Básicas
publisher.none.fl_str_mv Asociacion Espanola de Micologia
dc.source.none.fl_str_mv Revista Iberoamericana de Micologia
institution Universidad de Medellín
repository.name.fl_str_mv Repositorio Institucional Universidad de Medellin
repository.mail.fl_str_mv repositorio@udem.edu.co
_version_ 1814159159469277184
spelling 20192020-04-29T14:54:07Z2020-04-29T14:54:07Z11301406http://hdl.handle.net/11407/581210.1016/j.riam.2019.06.002Background: In a previous work we showed the feasibility of an interferon gamma release assay (IGRA) for detecting latent infection by Histoplasma capsulatum. While in that proof-of-concept study we used crude fungal extracts as antigens, the newest IGRAs developed for other infections are based on molecularly defined antigens, mostly on mixtures of immunogenic peptides. Aims: To identify proteins in H. capsulatum that might serve as molecularly defined antigens for an IGRA test. Methods: We surveyed the literature looking for known H. capsulatum-immunogenic proteins and assayed two of them as antigens in an IGRA test, in a study that involved 80 volunteers. Furthermore, we used several bioinformatics tools to identify specific H. capsulatum proteins and to analyze possible strategies for the design of H. capsulatum-specific immunogenic peptides. Results: Seven H. capsulatum-immunogenic proteins were retrieved from the literature. IGRA tests using either the heat shock protein 60 or the M antigen showed high sensitivities but low specificities, most likely due to the high sequence similarity with the corresponding orthologs in other pathogenic microorganisms. We identified around 2000 H. capsulatum-specific proteins, most of which remain unannotated. Class II T-cell epitope predictions for a small number of these proteins showed a great variability among different alleles, prompting for a brute force approach for peptide design. Conclusions: The H. capsulatum genome encodes a large number of distinctive proteins, which represent a valuable source of potential specific antigens for an IGRA test. Among them, the Cfp4 protein stands out as a very attractive candidate. © 2019 Asociación Española de MicologíaengspaAsociacion Espanola de MicologiaFacultad de Ciencias BásicasFacultad de Ciencias Básicashttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85075592310&doi=10.1016%2fj.riam.2019.06.002&partnerID=40&md5=af0fd57be13f4e5f724549fc8c674fa4364186191Aagaard, C., Brock, I., Olsen, A., Ottenhoff, T.H.M., Weldingh, K., Andersen, P., Mapping immune reactivity toward Rv2653 and Rv2654: two novel low-molecular-mass antigens found specifically in the Mycobacterium tuberculosis complex (2004) J Infect Dis, 189, pp. 812-819Adenis, A., Aznar, C., Couppié, P., Histoplasmosis in HIV-infected patients: a review of new developments and remaining gaps (2014) Curr Trop Med Rep, 1, pp. 119-128Albuquerque, P.C., Nakayasu, E.S., Rodrigues, M.L., Frases, S., Casadevall, A., Zancope-Oliveira, R.M., Vesicular transport in Histoplasma capsulatum: an effective mechanism for trans-cell wall transfer of proteins and lipids in ascomycetes (2008) Cell Microbiol, 10, pp. 1695-1710Allendoerfer, R., Deepe, G.S., Intrapulmonary response to Histoplasma capsulatum in gamma interferon knockout mice (1997) Infect Immun, 65, pp. 2564-2569Barcellini, L., Borroni, E., Brown, J., Brunetti, E., Codecasa, L., Cugnata, F., First independent evaluation of QuantiFERON-TB Plus performance (2016) Eur Respir J, 47, pp. 1587-1590Bendtsen, J.D., Jensen, L.J., Blom, N., Von Heijne, G., Brunak, S., Feature-based prediction of non-classical and leaderless protein secretion (2004) Protein Eng Des Sel, 17, pp. 349-356Chapey, E., Wallon, M., Debize, G., Rabilloud, M., Peyron, F., Diagnosis of congenital toxoplasmosis by using a whole-blood gamma interferon release assay (2010) J Clin Microbiol, 48, pp. 41-45Dammermann, W., Bentzien, F., Stiel, E.M., Kühne, C., Ullrich, S., zur Wiesch, J.S., Development of a novel IGRA assay to test T cell responsiveness to HBV antigens in whole blood of chronic hepatitis B patients (2015) J Transl Med, 13, p. 157Deepe, G.S., Histoplasma capsulatum (histoplasmosis) (2014) Mandell, Douglas, and Bennett's principles and practice of infectious diseases, pp. 2949-2962Dominguez, M.R., Silveira, E.L., de Vasconcelos, J.R., de Alencar, B.C., Machado, A.V., Bruna-Romero, O., Subdominant/cryptic CD8 T cell epitopes contribute to resistance against experimental infection with a human protozoan parasite (2011) PLoS ONE, 6, pp. 1-12Emanuelsson, O., Nielsen, H., Brunak, S., von Heijne, G., Predicting subcellular localization of proteins based on their N-terminal amino acid sequence (2000) J Mol Biol, 300, pp. 1005-1016Gidwani, K., Jones, S., Kumar, R., Boelaert, M., Sundar, S., Interferon-Gamma release assay (modified quantiFERON) as a potential marker of infection for Leishmania donovani, a proof of concept study (2011) PLoS Negl Trop Dis, 5, p. e1042Giulieri, S., Manuel, O., QuantiFERON®-CMV assay for the assessment of cytomegalovirus cell-mediated immunity (2011) Expert Rev Mol Diagn, 11, pp. 17-25Guimarães, A.J., Hamilton, A.J., de M Guedes, H.L., Nosanchuk, J.D., Zancopé-Oliveira, R.M., Biological function and molecular mapping of M antigen in yeast phase of Histoplasma capsulatum (2008) PLoS ONE, 3, p. e3449Guimarães, A.J., Frases, S., Gomez, F.J., Zancopé-Oliveira, R.M., Nosanchuk, J.D., Monoclonal antibodies to heat shock protein 60 alter the pathogenesis of Histoplasma capsulatum (2009) Infect Immun, 77, pp. 1357-1367Hober, D., Benyoucef, S., Chehadeh, W., Hober, D., Benyoucef, S., Chehadeh, W., Ex vivo interferon-gamma response to human immunodeficiency virus-1 derived peptides in human immunodeficiency virus-1 infected patients (2000) Scand J Immunol, 51, pp. 429-433Holbrook, E.D., Kemski, M.M., Richer, S.M., Wheat, L.J., Rappleye, C.A., Glycosylation and immunoreactivity of the Histoplasma capsulatum Cfp4 yeast-phase exoantigen (2014) Infect Immun, 82, pp. 4414-4425Horwath, M.C., Fecher, R.A., Deepe, G.S., Histoplasma capsulatum, lung infection and immunity (2015) Future Microbiol, 10, pp. 967-975Jensen, K.K., Andreatta, M., Marcatili, P., Buus, S., Greenbaum, J.A., Yan, Z., Improved methods for predicting peptide binding affinity to MHC class II molecules (2018) Immunology, 154, pp. 394-406Krogh, A., Larsson, B., Von Heijne, G., Sonnhammer, E.L.L., Predicting transmembrane protein topology with a hidden Markov model: application to complete genomes (2001) J Mol Biol, 305, pp. 567-580Li, L., Stoeckert, C.J., Roos, D.S., OrthoMCL: identification of ortholog groups for eukaryotic genomes (2003) Genome Res, 13, pp. 2178-2189Mazurek, G.H., Villarino, M.E., Guidelines for using the QuantiFERON-TB test for diagnosing latent Mycobacterium tuberculosis infection. Centers for Disease Control and Prevention (2003) MMWR Recomm Rep, 52, pp. 15-18Nel, J.S., Bartelt, L.A., van Duin, D., Lachiewicz, A.M., Endemic mycoses in solid organ transplant recipients (2018) Infect Dis Clin N Am, 32, pp. 667-685Rubio-Carrasquilla, M., Santa, C.D., Rendón, J.P., Botero-Garcés, J., Moreno, E., Cano, L.E., An interferon gamma release assay specific for Histoplasma capsulatum to detect asymptomatic infected individuals: a proof of concept study (2019) Med Mycol, 57, pp. 724-732Sifuentes-Osornio, J., Corzo-León, D.E., Ponce-De-León, L.A., Epidemiology of invasive fungal infections in Latin America (2012) Curr Fungal Infect Rep, 6, pp. 23-34Smith, J.G., Liu, X., Kaufhold, R.M., Clair, J., Caulfield, M.J., Development and validation of a gamma interferon ELISPOT assay for quantitation of cellular immune responses to varicella-zoster virus (2001) Clin Diagn Lab Immunol, 8, pp. 871-879Turgay, N., Balcioglu, I.C., Toz, S.O., Ozbel, Y., Jones, S.L., Short report: Quantiferon-Leishmania as an epidemiological tool for evaluating the exposure to Leishmania infection (2010) Am J Trop Med Hyg, 83, pp. 822-824Vergidis, P., Avery, R.K., Wheat, L.J., Dotson, J.L., Assi, M.A., Antoun, S.A., Histoplasmosis complicating tumor necrosis factor-? blocker therapy: a retrospective analysis of 98 cases (2015) Clin Infect Dis, 61, pp. 409-417Weir, R.E., Morgan, A.R., Britton, W.J., Butlin, C.R., Dockrell, H.M., Development of a whole blood assay to measure T cell responses to leprosy: a new tool for immuno-epidemiological field studies of leprosy immunity (1994) J Immunol Methods, 176, pp. 93-101Revista Iberoamericana de MicologiaHistoplasma capsulatumIGRAImmunogenic proteinsMolecularly defined antigensT-cell epitopesalcohol dehydrogenaseankyrin repeat proteinbeta lactamasechaperonin 60DUF636 domain containing proteinepitopefungus antigenM antigenproteoglycansynthetic peptideunclassified drugalleleamino acid sequenceantigen detectionantigenic variationArticlecontrolled studyHistoplasma capsulatumhumanimmunogenicityinterferon gamma release assaynonhumanorthologypathogenicityprotein analysissensitivity and specificityvolunteerIdentifying molecularly defined antigens for a Histoplasma capsulatum-specific interferon gamma release assay [Identificación de antígenos definidos molecularmente para un ensayo de liberación de interferón-gamma específico para Histoplasma capsulatum]Articleinfo:eu-repo/semantics/articlehttp://purl.org/coar/version/c_970fb48d4fbd8a85http://purl.org/coar/resource_type/c_6501http://purl.org/coar/resource_type/c_2df8fbb1Rubio-Carrasquilla, M., Grupo de Micología Médica y Experimental, Corporación para Investigaciones Biológicas (CIB), Medellín, Colombia, Instituto de Biología, Universidad de Antioquia, Medellín, Colombia; Ochoa, R., Programa de Estudio y Control de Enfermedades Tropicales PECET, Universidad de Antioquia, Medellín, Colombia; Santa, C., Universidad Nacional de Colombia, Sede Medellín, Medellín, Colombia; Guimarães, A.J., Depto de Microbiologia e Parasitologia, Universidade Federal Fluminense, Niterói, RJ, Brazil; Cano, L.E., Grupo de Micología Médica y Experimental, Corporación para Investigaciones Biológicas (CIB), Medellín, Colombia, Escuela de Microbiología, Universidad de Antioquia, Medellín, Colombia; Moreno, E., Facultad de Ciencias Básicas, Universidad de Medellín, Medellín, Colombiahttp://purl.org/coar/access_right/c_16ecRubio-Carrasquilla M.Ochoa R.Santa C.Guimarães A.J.Cano L.E.Moreno E.11407/5812oai:repository.udem.edu.co:11407/58122020-12-15 15:05:30.349Repositorio Institucional Universidad de Medellinrepositorio@udem.edu.co