Elucidating the 3D Structure of a Surface Membrane Antigen from <i<Trypanosoma cruzi</i< as a Serodiagnostic Biomarker of Chagas Disease

Chagas disease (CD) is a vector-borne parasitosis, caused by the protozoan parasite <i<Trypanosoma cruzi</i<, that affects millions of people worldwide. Although endemic in South America, CD is emerging throughout the world due to climate change and increased immigratory flux of infected...
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Autor*in:	Flavio Di Pisa [verfasserIn] Stefano De Benedetti [verfasserIn] Enrico Mario Alessandro Fassi [verfasserIn] Mauro Bombaci [verfasserIn] Renata Grifantini [verfasserIn] Angelo Musicò [verfasserIn] Roberto Frigerio [verfasserIn] Angela Pontillo [verfasserIn] Cinzia Rigo [verfasserIn] Sandra Abelli [verfasserIn] Romualdo Grande [verfasserIn] Nadia Zanchetta [verfasserIn] Davide Mileto [verfasserIn] Alessandro Mancon [verfasserIn] Alberto Rizzo [verfasserIn] Alessandro Gori [verfasserIn] Marina Cretich [verfasserIn] Giorgio Colombo [verfasserIn] Martino Bolognesi [verfasserIn] Louise Jane Gourlay [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	Chagas disease neglected tropical disease structural vaccinology peptide microarray in silico epitope mapping

Übergeordnetes Werk:	In: Vaccines - MDPI AG, 2013, 10(2022), 1, p 71
Übergeordnetes Werk:	volume:10 ; year:2022 ; number:1, p 71

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3390/vaccines10010071

Katalog-ID:	DOAJ085081221

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520			\|a Chagas disease (CD) is a vector-borne parasitosis, caused by the protozoan parasite <i<Trypanosoma cruzi</i<, that affects millions of people worldwide. Although endemic in South America, CD is emerging throughout the world due to climate change and increased immigratory flux of infected people to non-endemic regions. Containing of the diffusion of CD is challenged by the asymptomatic nature of the disease in early infection stages and by the lack of a rapid and effective diagnostic test. With the aim of designing new serodiagnostic molecules to be implemented in a microarray-based diagnostic set-up for early screening of CD, herein, we report the recombinant production of the extracellular domain of a surface membrane antigen from <i<T. cruzi</i< (<i<Tc</i<SMP) and confirm its ability to detect plasma antibodies from infected patients. Moreover, we describe its high-resolution (1.62 Å) crystal structure, to which in silico epitope predictions were applied in order to locate the most immunoreactive regions of <i<Tc</i<SMP in order to guide the design of epitopes that may be used as an alternative to the full-length antigen for CD diagnosis. Two putative, linear epitopes, belonging to the same immunogenic region, were synthesized as free peptides, and their immunological properties were tested in vitro. Although both peptides were shown to adopt a structural conformation that allowed their recognition by polyclonal antibodies raised against the recombinant protein, they were not serodiagnostic for <i<T. cruzi</i< infections. Nevertheless, they represent good starting points for further iterative structure-based (re)design cycles.
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allfields	10.3390/vaccines10010071 doi (DE-627)DOAJ085081221 (DE-599)DOAJ3254ae672fc54ec1b58f7ebdf0acafb0 DE-627 ger DE-627 rakwb eng Flavio Di Pisa verfasserin aut Elucidating the 3D Structure of a Surface Membrane Antigen from <i<Trypanosoma cruzi</i< as a Serodiagnostic Biomarker of Chagas Disease 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Chagas disease (CD) is a vector-borne parasitosis, caused by the protozoan parasite <i<Trypanosoma cruzi</i<, that affects millions of people worldwide. Although endemic in South America, CD is emerging throughout the world due to climate change and increased immigratory flux of infected people to non-endemic regions. Containing of the diffusion of CD is challenged by the asymptomatic nature of the disease in early infection stages and by the lack of a rapid and effective diagnostic test. With the aim of designing new serodiagnostic molecules to be implemented in a microarray-based diagnostic set-up for early screening of CD, herein, we report the recombinant production of the extracellular domain of a surface membrane antigen from <i<T. cruzi</i< (<i<Tc</i<SMP) and confirm its ability to detect plasma antibodies from infected patients. Moreover, we describe its high-resolution (1.62 Å) crystal structure, to which in silico epitope predictions were applied in order to locate the most immunoreactive regions of <i<Tc</i<SMP in order to guide the design of epitopes that may be used as an alternative to the full-length antigen for CD diagnosis. Two putative, linear epitopes, belonging to the same immunogenic region, were synthesized as free peptides, and their immunological properties were tested in vitro. Although both peptides were shown to adopt a structural conformation that allowed their recognition by polyclonal antibodies raised against the recombinant protein, they were not serodiagnostic for <i<T. cruzi</i< infections. Nevertheless, they represent good starting points for further iterative structure-based (re)design cycles. Chagas disease <i<Trypanosoma cruzi</i< neglected tropical disease structural vaccinology peptide microarray in silico epitope mapping Medicine R Stefano De Benedetti verfasserin aut Enrico Mario Alessandro Fassi verfasserin aut Mauro Bombaci verfasserin aut Renata Grifantini verfasserin aut Angelo Musicò verfasserin aut Roberto Frigerio verfasserin aut Angela Pontillo verfasserin aut Cinzia Rigo verfasserin aut Sandra Abelli verfasserin aut Romualdo Grande verfasserin aut Nadia Zanchetta verfasserin aut Davide Mileto verfasserin aut Alessandro Mancon verfasserin aut Alberto Rizzo verfasserin aut Alessandro Gori verfasserin aut Marina Cretich verfasserin aut Giorgio Colombo verfasserin aut Martino Bolognesi verfasserin aut Louise Jane Gourlay verfasserin aut In Vaccines MDPI AG, 2013 10(2022), 1, p 71 (DE-627)736559205 (DE-600)2703319-3 2076393X nnns volume:10 year:2022 number:1, p 71 https://doi.org/10.3390/vaccines10010071 kostenfrei https://doaj.org/article/3254ae672fc54ec1b58f7ebdf0acafb0 kostenfrei https://www.mdpi.com/2076-393X/10/1/71 kostenfrei https://doaj.org/toc/2076-393X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2022 1, p 71
spelling	10.3390/vaccines10010071 doi (DE-627)DOAJ085081221 (DE-599)DOAJ3254ae672fc54ec1b58f7ebdf0acafb0 DE-627 ger DE-627 rakwb eng Flavio Di Pisa verfasserin aut Elucidating the 3D Structure of a Surface Membrane Antigen from <i<Trypanosoma cruzi</i< as a Serodiagnostic Biomarker of Chagas Disease 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Chagas disease (CD) is a vector-borne parasitosis, caused by the protozoan parasite <i<Trypanosoma cruzi</i<, that affects millions of people worldwide. Although endemic in South America, CD is emerging throughout the world due to climate change and increased immigratory flux of infected people to non-endemic regions. Containing of the diffusion of CD is challenged by the asymptomatic nature of the disease in early infection stages and by the lack of a rapid and effective diagnostic test. With the aim of designing new serodiagnostic molecules to be implemented in a microarray-based diagnostic set-up for early screening of CD, herein, we report the recombinant production of the extracellular domain of a surface membrane antigen from <i<T. cruzi</i< (<i<Tc</i<SMP) and confirm its ability to detect plasma antibodies from infected patients. Moreover, we describe its high-resolution (1.62 Å) crystal structure, to which in silico epitope predictions were applied in order to locate the most immunoreactive regions of <i<Tc</i<SMP in order to guide the design of epitopes that may be used as an alternative to the full-length antigen for CD diagnosis. Two putative, linear epitopes, belonging to the same immunogenic region, were synthesized as free peptides, and their immunological properties were tested in vitro. Although both peptides were shown to adopt a structural conformation that allowed their recognition by polyclonal antibodies raised against the recombinant protein, they were not serodiagnostic for <i<T. cruzi</i< infections. Nevertheless, they represent good starting points for further iterative structure-based (re)design cycles. Chagas disease <i<Trypanosoma cruzi</i< neglected tropical disease structural vaccinology peptide microarray in silico epitope mapping Medicine R Stefano De Benedetti verfasserin aut Enrico Mario Alessandro Fassi verfasserin aut Mauro Bombaci verfasserin aut Renata Grifantini verfasserin aut Angelo Musicò verfasserin aut Roberto Frigerio verfasserin aut Angela Pontillo verfasserin aut Cinzia Rigo verfasserin aut Sandra Abelli verfasserin aut Romualdo Grande verfasserin aut Nadia Zanchetta verfasserin aut Davide Mileto verfasserin aut Alessandro Mancon verfasserin aut Alberto Rizzo verfasserin aut Alessandro Gori verfasserin aut Marina Cretich verfasserin aut Giorgio Colombo verfasserin aut Martino Bolognesi verfasserin aut Louise Jane Gourlay verfasserin aut In Vaccines MDPI AG, 2013 10(2022), 1, p 71 (DE-627)736559205 (DE-600)2703319-3 2076393X nnns volume:10 year:2022 number:1, p 71 https://doi.org/10.3390/vaccines10010071 kostenfrei https://doaj.org/article/3254ae672fc54ec1b58f7ebdf0acafb0 kostenfrei https://www.mdpi.com/2076-393X/10/1/71 kostenfrei https://doaj.org/toc/2076-393X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2022 1, p 71
allfields_unstemmed	10.3390/vaccines10010071 doi (DE-627)DOAJ085081221 (DE-599)DOAJ3254ae672fc54ec1b58f7ebdf0acafb0 DE-627 ger DE-627 rakwb eng Flavio Di Pisa verfasserin aut Elucidating the 3D Structure of a Surface Membrane Antigen from <i<Trypanosoma cruzi</i< as a Serodiagnostic Biomarker of Chagas Disease 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Chagas disease (CD) is a vector-borne parasitosis, caused by the protozoan parasite <i<Trypanosoma cruzi</i<, that affects millions of people worldwide. Although endemic in South America, CD is emerging throughout the world due to climate change and increased immigratory flux of infected people to non-endemic regions. Containing of the diffusion of CD is challenged by the asymptomatic nature of the disease in early infection stages and by the lack of a rapid and effective diagnostic test. With the aim of designing new serodiagnostic molecules to be implemented in a microarray-based diagnostic set-up for early screening of CD, herein, we report the recombinant production of the extracellular domain of a surface membrane antigen from <i<T. cruzi</i< (<i<Tc</i<SMP) and confirm its ability to detect plasma antibodies from infected patients. Moreover, we describe its high-resolution (1.62 Å) crystal structure, to which in silico epitope predictions were applied in order to locate the most immunoreactive regions of <i<Tc</i<SMP in order to guide the design of epitopes that may be used as an alternative to the full-length antigen for CD diagnosis. Two putative, linear epitopes, belonging to the same immunogenic region, were synthesized as free peptides, and their immunological properties were tested in vitro. Although both peptides were shown to adopt a structural conformation that allowed their recognition by polyclonal antibodies raised against the recombinant protein, they were not serodiagnostic for <i<T. cruzi</i< infections. Nevertheless, they represent good starting points for further iterative structure-based (re)design cycles. Chagas disease <i<Trypanosoma cruzi</i< neglected tropical disease structural vaccinology peptide microarray in silico epitope mapping Medicine R Stefano De Benedetti verfasserin aut Enrico Mario Alessandro Fassi verfasserin aut Mauro Bombaci verfasserin aut Renata Grifantini verfasserin aut Angelo Musicò verfasserin aut Roberto Frigerio verfasserin aut Angela Pontillo verfasserin aut Cinzia Rigo verfasserin aut Sandra Abelli verfasserin aut Romualdo Grande verfasserin aut Nadia Zanchetta verfasserin aut Davide Mileto verfasserin aut Alessandro Mancon verfasserin aut Alberto Rizzo verfasserin aut Alessandro Gori verfasserin aut Marina Cretich verfasserin aut Giorgio Colombo verfasserin aut Martino Bolognesi verfasserin aut Louise Jane Gourlay verfasserin aut In Vaccines MDPI AG, 2013 10(2022), 1, p 71 (DE-627)736559205 (DE-600)2703319-3 2076393X nnns volume:10 year:2022 number:1, p 71 https://doi.org/10.3390/vaccines10010071 kostenfrei https://doaj.org/article/3254ae672fc54ec1b58f7ebdf0acafb0 kostenfrei https://www.mdpi.com/2076-393X/10/1/71 kostenfrei https://doaj.org/toc/2076-393X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2022 1, p 71
allfieldsGer	10.3390/vaccines10010071 doi (DE-627)DOAJ085081221 (DE-599)DOAJ3254ae672fc54ec1b58f7ebdf0acafb0 DE-627 ger DE-627 rakwb eng Flavio Di Pisa verfasserin aut Elucidating the 3D Structure of a Surface Membrane Antigen from <i<Trypanosoma cruzi</i< as a Serodiagnostic Biomarker of Chagas Disease 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Chagas disease (CD) is a vector-borne parasitosis, caused by the protozoan parasite <i<Trypanosoma cruzi</i<, that affects millions of people worldwide. Although endemic in South America, CD is emerging throughout the world due to climate change and increased immigratory flux of infected people to non-endemic regions. Containing of the diffusion of CD is challenged by the asymptomatic nature of the disease in early infection stages and by the lack of a rapid and effective diagnostic test. With the aim of designing new serodiagnostic molecules to be implemented in a microarray-based diagnostic set-up for early screening of CD, herein, we report the recombinant production of the extracellular domain of a surface membrane antigen from <i<T. cruzi</i< (<i<Tc</i<SMP) and confirm its ability to detect plasma antibodies from infected patients. Moreover, we describe its high-resolution (1.62 Å) crystal structure, to which in silico epitope predictions were applied in order to locate the most immunoreactive regions of <i<Tc</i<SMP in order to guide the design of epitopes that may be used as an alternative to the full-length antigen for CD diagnosis. Two putative, linear epitopes, belonging to the same immunogenic region, were synthesized as free peptides, and their immunological properties were tested in vitro. Although both peptides were shown to adopt a structural conformation that allowed their recognition by polyclonal antibodies raised against the recombinant protein, they were not serodiagnostic for <i<T. cruzi</i< infections. Nevertheless, they represent good starting points for further iterative structure-based (re)design cycles. Chagas disease <i<Trypanosoma cruzi</i< neglected tropical disease structural vaccinology peptide microarray in silico epitope mapping Medicine R Stefano De Benedetti verfasserin aut Enrico Mario Alessandro Fassi verfasserin aut Mauro Bombaci verfasserin aut Renata Grifantini verfasserin aut Angelo Musicò verfasserin aut Roberto Frigerio verfasserin aut Angela Pontillo verfasserin aut Cinzia Rigo verfasserin aut Sandra Abelli verfasserin aut Romualdo Grande verfasserin aut Nadia Zanchetta verfasserin aut Davide Mileto verfasserin aut Alessandro Mancon verfasserin aut Alberto Rizzo verfasserin aut Alessandro Gori verfasserin aut Marina Cretich verfasserin aut Giorgio Colombo verfasserin aut Martino Bolognesi verfasserin aut Louise Jane Gourlay verfasserin aut In Vaccines MDPI AG, 2013 10(2022), 1, p 71 (DE-627)736559205 (DE-600)2703319-3 2076393X nnns volume:10 year:2022 number:1, p 71 https://doi.org/10.3390/vaccines10010071 kostenfrei https://doaj.org/article/3254ae672fc54ec1b58f7ebdf0acafb0 kostenfrei https://www.mdpi.com/2076-393X/10/1/71 kostenfrei https://doaj.org/toc/2076-393X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2022 1, p 71
allfieldsSound	10.3390/vaccines10010071 doi (DE-627)DOAJ085081221 (DE-599)DOAJ3254ae672fc54ec1b58f7ebdf0acafb0 DE-627 ger DE-627 rakwb eng Flavio Di Pisa verfasserin aut Elucidating the 3D Structure of a Surface Membrane Antigen from <i<Trypanosoma cruzi</i< as a Serodiagnostic Biomarker of Chagas Disease 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Chagas disease (CD) is a vector-borne parasitosis, caused by the protozoan parasite <i<Trypanosoma cruzi</i<, that affects millions of people worldwide. Although endemic in South America, CD is emerging throughout the world due to climate change and increased immigratory flux of infected people to non-endemic regions. Containing of the diffusion of CD is challenged by the asymptomatic nature of the disease in early infection stages and by the lack of a rapid and effective diagnostic test. With the aim of designing new serodiagnostic molecules to be implemented in a microarray-based diagnostic set-up for early screening of CD, herein, we report the recombinant production of the extracellular domain of a surface membrane antigen from <i<T. cruzi</i< (<i<Tc</i<SMP) and confirm its ability to detect plasma antibodies from infected patients. Moreover, we describe its high-resolution (1.62 Å) crystal structure, to which in silico epitope predictions were applied in order to locate the most immunoreactive regions of <i<Tc</i<SMP in order to guide the design of epitopes that may be used as an alternative to the full-length antigen for CD diagnosis. Two putative, linear epitopes, belonging to the same immunogenic region, were synthesized as free peptides, and their immunological properties were tested in vitro. Although both peptides were shown to adopt a structural conformation that allowed their recognition by polyclonal antibodies raised against the recombinant protein, they were not serodiagnostic for <i<T. cruzi</i< infections. Nevertheless, they represent good starting points for further iterative structure-based (re)design cycles. Chagas disease <i<Trypanosoma cruzi</i< neglected tropical disease structural vaccinology peptide microarray in silico epitope mapping Medicine R Stefano De Benedetti verfasserin aut Enrico Mario Alessandro Fassi verfasserin aut Mauro Bombaci verfasserin aut Renata Grifantini verfasserin aut Angelo Musicò verfasserin aut Roberto Frigerio verfasserin aut Angela Pontillo verfasserin aut Cinzia Rigo verfasserin aut Sandra Abelli verfasserin aut Romualdo Grande verfasserin aut Nadia Zanchetta verfasserin aut Davide Mileto verfasserin aut Alessandro Mancon verfasserin aut Alberto Rizzo verfasserin aut Alessandro Gori verfasserin aut Marina Cretich verfasserin aut Giorgio Colombo verfasserin aut Martino Bolognesi verfasserin aut Louise Jane Gourlay verfasserin aut In Vaccines MDPI AG, 2013 10(2022), 1, p 71 (DE-627)736559205 (DE-600)2703319-3 2076393X nnns volume:10 year:2022 number:1, p 71 https://doi.org/10.3390/vaccines10010071 kostenfrei https://doaj.org/article/3254ae672fc54ec1b58f7ebdf0acafb0 kostenfrei https://www.mdpi.com/2076-393X/10/1/71 kostenfrei https://doaj.org/toc/2076-393X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2022 1, p 71
language	English
source	In Vaccines 10(2022), 1, p 71 volume:10 year:2022 number:1, p 71
sourceStr	In Vaccines 10(2022), 1, p 71 volume:10 year:2022 number:1, p 71
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Chagas disease <i<Trypanosoma cruzi</i< neglected tropical disease structural vaccinology peptide microarray in silico epitope mapping Medicine R
isfreeaccess_bool	true
container_title	Vaccines
authorswithroles_txt_mv	Flavio Di Pisa @@aut@@ Stefano De Benedetti @@aut@@ Enrico Mario Alessandro Fassi @@aut@@ Mauro Bombaci @@aut@@ Renata Grifantini @@aut@@ Angelo Musicò @@aut@@ Roberto Frigerio @@aut@@ Angela Pontillo @@aut@@ Cinzia Rigo @@aut@@ Sandra Abelli @@aut@@ Romualdo Grande @@aut@@ Nadia Zanchetta @@aut@@ Davide Mileto @@aut@@ Alessandro Mancon @@aut@@ Alberto Rizzo @@aut@@ Alessandro Gori @@aut@@ Marina Cretich @@aut@@ Giorgio Colombo @@aut@@ Martino Bolognesi @@aut@@ Louise Jane Gourlay @@aut@@
publishDateDaySort_date	2022-01-01T00:00:00Z
hierarchy_top_id	736559205
id	DOAJ085081221
language_de	englisch
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author	Flavio Di Pisa
spellingShingle	Flavio Di Pisa misc Chagas disease misc <i<Trypanosoma cruzi</i< misc neglected tropical disease misc structural vaccinology misc peptide microarray misc in silico epitope mapping misc Medicine misc R Elucidating the 3D Structure of a Surface Membrane Antigen from <i<Trypanosoma cruzi</i< as a Serodiagnostic Biomarker of Chagas Disease
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topic_title	Elucidating the 3D Structure of a Surface Membrane Antigen from <i<Trypanosoma cruzi</i< as a Serodiagnostic Biomarker of Chagas Disease Chagas disease <i<Trypanosoma cruzi</i< neglected tropical disease structural vaccinology peptide microarray in silico epitope mapping
topic	misc Chagas disease misc <i<Trypanosoma cruzi</i< misc neglected tropical disease misc structural vaccinology misc peptide microarray misc in silico epitope mapping misc Medicine misc R
topic_unstemmed	misc Chagas disease misc <i<Trypanosoma cruzi</i< misc neglected tropical disease misc structural vaccinology misc peptide microarray misc in silico epitope mapping misc Medicine misc R
topic_browse	misc Chagas disease misc <i<Trypanosoma cruzi</i< misc neglected tropical disease misc structural vaccinology misc peptide microarray misc in silico epitope mapping misc Medicine misc R
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title	Elucidating the 3D Structure of a Surface Membrane Antigen from <i<Trypanosoma cruzi</i< as a Serodiagnostic Biomarker of Chagas Disease
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title_full	Elucidating the 3D Structure of a Surface Membrane Antigen from <i<Trypanosoma cruzi</i< as a Serodiagnostic Biomarker of Chagas Disease
author_sort	Flavio Di Pisa
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author_browse	Flavio Di Pisa Stefano De Benedetti Enrico Mario Alessandro Fassi Mauro Bombaci Renata Grifantini Angelo Musicò Roberto Frigerio Angela Pontillo Cinzia Rigo Sandra Abelli Romualdo Grande Nadia Zanchetta Davide Mileto Alessandro Mancon Alberto Rizzo Alessandro Gori Marina Cretich Giorgio Colombo Martino Bolognesi Louise Jane Gourlay
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author-letter	Flavio Di Pisa
doi_str_mv	10.3390/vaccines10010071
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title_sort	elucidating the 3d structure of a surface membrane antigen from <i<trypanosoma cruzi</i< as a serodiagnostic biomarker of chagas disease
title_auth	Elucidating the 3D Structure of a Surface Membrane Antigen from <i<Trypanosoma cruzi</i< as a Serodiagnostic Biomarker of Chagas Disease
abstract	Chagas disease (CD) is a vector-borne parasitosis, caused by the protozoan parasite <i<Trypanosoma cruzi</i<, that affects millions of people worldwide. Although endemic in South America, CD is emerging throughout the world due to climate change and increased immigratory flux of infected people to non-endemic regions. Containing of the diffusion of CD is challenged by the asymptomatic nature of the disease in early infection stages and by the lack of a rapid and effective diagnostic test. With the aim of designing new serodiagnostic molecules to be implemented in a microarray-based diagnostic set-up for early screening of CD, herein, we report the recombinant production of the extracellular domain of a surface membrane antigen from <i<T. cruzi</i< (<i<Tc</i<SMP) and confirm its ability to detect plasma antibodies from infected patients. Moreover, we describe its high-resolution (1.62 Å) crystal structure, to which in silico epitope predictions were applied in order to locate the most immunoreactive regions of <i<Tc</i<SMP in order to guide the design of epitopes that may be used as an alternative to the full-length antigen for CD diagnosis. Two putative, linear epitopes, belonging to the same immunogenic region, were synthesized as free peptides, and their immunological properties were tested in vitro. Although both peptides were shown to adopt a structural conformation that allowed their recognition by polyclonal antibodies raised against the recombinant protein, they were not serodiagnostic for <i<T. cruzi</i< infections. Nevertheless, they represent good starting points for further iterative structure-based (re)design cycles.
abstractGer	Chagas disease (CD) is a vector-borne parasitosis, caused by the protozoan parasite <i<Trypanosoma cruzi</i<, that affects millions of people worldwide. Although endemic in South America, CD is emerging throughout the world due to climate change and increased immigratory flux of infected people to non-endemic regions. Containing of the diffusion of CD is challenged by the asymptomatic nature of the disease in early infection stages and by the lack of a rapid and effective diagnostic test. With the aim of designing new serodiagnostic molecules to be implemented in a microarray-based diagnostic set-up for early screening of CD, herein, we report the recombinant production of the extracellular domain of a surface membrane antigen from <i<T. cruzi</i< (<i<Tc</i<SMP) and confirm its ability to detect plasma antibodies from infected patients. Moreover, we describe its high-resolution (1.62 Å) crystal structure, to which in silico epitope predictions were applied in order to locate the most immunoreactive regions of <i<Tc</i<SMP in order to guide the design of epitopes that may be used as an alternative to the full-length antigen for CD diagnosis. Two putative, linear epitopes, belonging to the same immunogenic region, were synthesized as free peptides, and their immunological properties were tested in vitro. Although both peptides were shown to adopt a structural conformation that allowed their recognition by polyclonal antibodies raised against the recombinant protein, they were not serodiagnostic for <i<T. cruzi</i< infections. Nevertheless, they represent good starting points for further iterative structure-based (re)design cycles.
abstract_unstemmed	Chagas disease (CD) is a vector-borne parasitosis, caused by the protozoan parasite <i<Trypanosoma cruzi</i<, that affects millions of people worldwide. Although endemic in South America, CD is emerging throughout the world due to climate change and increased immigratory flux of infected people to non-endemic regions. Containing of the diffusion of CD is challenged by the asymptomatic nature of the disease in early infection stages and by the lack of a rapid and effective diagnostic test. With the aim of designing new serodiagnostic molecules to be implemented in a microarray-based diagnostic set-up for early screening of CD, herein, we report the recombinant production of the extracellular domain of a surface membrane antigen from <i<T. cruzi</i< (<i<Tc</i<SMP) and confirm its ability to detect plasma antibodies from infected patients. Moreover, we describe its high-resolution (1.62 Å) crystal structure, to which in silico epitope predictions were applied in order to locate the most immunoreactive regions of <i<Tc</i<SMP in order to guide the design of epitopes that may be used as an alternative to the full-length antigen for CD diagnosis. Two putative, linear epitopes, belonging to the same immunogenic region, were synthesized as free peptides, and their immunological properties were tested in vitro. Although both peptides were shown to adopt a structural conformation that allowed their recognition by polyclonal antibodies raised against the recombinant protein, they were not serodiagnostic for <i<T. cruzi</i< infections. Nevertheless, they represent good starting points for further iterative structure-based (re)design cycles.
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title_short	Elucidating the 3D Structure of a Surface Membrane Antigen from <i<Trypanosoma cruzi</i< as a Serodiagnostic Biomarker of Chagas Disease
url	https://doi.org/10.3390/vaccines10010071 https://doaj.org/article/3254ae672fc54ec1b58f7ebdf0acafb0 https://www.mdpi.com/2076-393X/10/1/71 https://doaj.org/toc/2076-393X
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Elucidating the 3D Structure of a Surface Membrane Antigen from <i<Trypanosoma cruzi</i< as a Serodiagnostic Biomarker of Chagas Disease

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