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Sensitive and specific serodiagnosis of tegumentary leishmaniasis using a new chimeric protein based on specific B-cell epitopes of Leishmania antigenic proteins

Sensitive and specific serodiagnosis of tegumentary leishmaniasis using a new chimeric protein based on specific B-cell epitopes of Leishmania antigenic proteins
Sensitive and specific serodiagnosis of tegumentary leishmaniasis using a new chimeric protein based on specific B-cell epitopes of Leishmania antigenic proteins
Serological tests used for the diagnosis of tegumentary leishmaniasis (TL) presents problems, mainly related to their variable sensitivity and/or specificity, which can be caused by low levels of antileishmanial antibodies or by presence of cross-reactive diseases, respectively. In this context, the search for new antigenic candidates presenting higher sensitivity and specificity is urgently required. In the present study, the amino acid sequences of the LiHyT, LiHyD, LiHyV, and LiHyP proteins, which were previously showed to be antigenic in the visceral leishmaniasis (VL), were evaluated and eight B-cell epitopes were predicted and used for construction of gene codifying a chimeric protein called ChimLeish. The protein was expressed, purified and evaluated as a recombinant antigen in ELISA (Enzyme-Linked Immunosorbent Assay) for the diagnosis of TL. The own B cell epitopes used to construct the chimera were synthetized and also evaluated as antigens, as well as a soluble Leishmania braziliensis antigenic extract (SLA). Results showed that ChimLeish presented 100% sensitivity and specificity to diagnose TL, while synthetic peptides showed sensitivity varying from 9.1% to 90.9%, while specificity reached from 98.3% to 99.1%. SLA showed sensitivity and specificity of 18.2% and 98.3%, respectively. A preliminary prognostic evaluation showed that anti-ChimLeish IgG antibodies declined in significant levels, when serological reactivity was compared before and six months after treatment, suggesting also a possible prognostic role of this antigen for TL.
Antibodies, Protozoan, Antigens, Protozoan/genetics, Enzyme-Linked Immunosorbent Assay, Epitopes, B-Lymphocyte/genetics, Humans, Leishmania/genetics, Leishmaniasis, Recombinant Fusion Proteins/genetics, Sensitivity and Specificity, Serologic Tests
0882-4010
105341
Galvani, Nathalia C
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Machado, Amanda S
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Lage, Daniela P
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Martins, Vívian T
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de Oliveira, Daysiane
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Freitas, Camila S
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Vale, Danniele L
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Fernandes, Bruna B
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Oliveira-da-Silva, João A
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Reis, Thiago A R
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Santos, Thaís T O
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Ramos, Fernanda F
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Bandeira, Raquel S
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Ludolf, Fernanda
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Tavares, Grasiele S V
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Guimarães, Nathalia S
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Tupinambás, Unaí
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Chávez-Fumagalli, Miguel A
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Humbert, Maria V
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Gonçalves, Denise U
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Christodoulides, Myron
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Machado-de-Ávila, Ricardo A
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Coelho, Eduardo A F
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Galvani, Nathalia C
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Machado, Amanda S
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Lage, Daniela P
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Martins, Vívian T
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de Oliveira, Daysiane
ae379cce-737b-4f4b-b04a-41f2bfd94fcd
Freitas, Camila S
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Vale, Danniele L
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Fernandes, Bruna B
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Oliveira-da-Silva, João A
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Reis, Thiago A R
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Santos, Thaís T O
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Ramos, Fernanda F
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Bandeira, Raquel S
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Ludolf, Fernanda
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Tavares, Grasiele S V
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Guimarães, Nathalia S
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Tupinambás, Unaí
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Chávez-Fumagalli, Miguel A
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Humbert, Maria V
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Gonçalves, Denise U
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Christodoulides, Myron
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Machado-de-Ávila, Ricardo A
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Coelho, Eduardo A F
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Galvani, Nathalia C, Machado, Amanda S, Lage, Daniela P, Martins, Vívian T, de Oliveira, Daysiane, Freitas, Camila S, Vale, Danniele L, Fernandes, Bruna B, Oliveira-da-Silva, João A, Reis, Thiago A R, Santos, Thaís T O, Ramos, Fernanda F, Bandeira, Raquel S, Ludolf, Fernanda, Tavares, Grasiele S V, Guimarães, Nathalia S, Tupinambás, Unaí, Chávez-Fumagalli, Miguel A, Humbert, Maria V, Gonçalves, Denise U, Christodoulides, Myron, Machado-de-Ávila, Ricardo A and Coelho, Eduardo A F (2021) Sensitive and specific serodiagnosis of tegumentary leishmaniasis using a new chimeric protein based on specific B-cell epitopes of Leishmania antigenic proteins. Microbial Pathogenesis, 162, 105341. (doi:10.1016/j.micpath.2021.105341).

Record type: Article

Abstract

Serological tests used for the diagnosis of tegumentary leishmaniasis (TL) presents problems, mainly related to their variable sensitivity and/or specificity, which can be caused by low levels of antileishmanial antibodies or by presence of cross-reactive diseases, respectively. In this context, the search for new antigenic candidates presenting higher sensitivity and specificity is urgently required. In the present study, the amino acid sequences of the LiHyT, LiHyD, LiHyV, and LiHyP proteins, which were previously showed to be antigenic in the visceral leishmaniasis (VL), were evaluated and eight B-cell epitopes were predicted and used for construction of gene codifying a chimeric protein called ChimLeish. The protein was expressed, purified and evaluated as a recombinant antigen in ELISA (Enzyme-Linked Immunosorbent Assay) for the diagnosis of TL. The own B cell epitopes used to construct the chimera were synthetized and also evaluated as antigens, as well as a soluble Leishmania braziliensis antigenic extract (SLA). Results showed that ChimLeish presented 100% sensitivity and specificity to diagnose TL, while synthetic peptides showed sensitivity varying from 9.1% to 90.9%, while specificity reached from 98.3% to 99.1%. SLA showed sensitivity and specificity of 18.2% and 98.3%, respectively. A preliminary prognostic evaluation showed that anti-ChimLeish IgG antibodies declined in significant levels, when serological reactivity was compared before and six months after treatment, suggesting also a possible prognostic role of this antigen for TL.

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Accepted/In Press date: 29 November 2021
e-pub ahead of print date: 6 December 2021
Published date: 8 December 2021
Keywords: Antibodies, Protozoan, Antigens, Protozoan/genetics, Enzyme-Linked Immunosorbent Assay, Epitopes, B-Lymphocyte/genetics, Humans, Leishmania/genetics, Leishmaniasis, Recombinant Fusion Proteins/genetics, Sensitivity and Specificity, Serologic Tests

Identifiers

Local EPrints ID: 458011
URI: http://eprints.soton.ac.uk/id/eprint/458011
ISSN: 0882-4010
PURE UUID: fc5b665e-2c28-48bf-a1d3-86fcc5b1ca6c
ORCID for Maria V Humbert: ORCID iD orcid.org/0000-0002-5728-6981
ORCID for Myron Christodoulides: ORCID iD orcid.org/0000-0002-9663-4731

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Date deposited: 24 Jun 2022 17:33
Last modified: 17 Mar 2024 07:21

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Contributors

Author: Nathalia C Galvani
Author: Amanda S Machado
Author: Daniela P Lage
Author: Vívian T Martins
Author: Daysiane de Oliveira
Author: Camila S Freitas
Author: Danniele L Vale
Author: Bruna B Fernandes
Author: João A Oliveira-da-Silva
Author: Thiago A R Reis
Author: Thaís T O Santos
Author: Fernanda F Ramos
Author: Raquel S Bandeira
Author: Fernanda Ludolf
Author: Grasiele S V Tavares
Author: Nathalia S Guimarães
Author: Unaí Tupinambás
Author: Miguel A Chávez-Fumagalli
Author: Maria V Humbert ORCID iD
Author: Denise U Gonçalves
Author: Ricardo A Machado-de-Ávila
Author: Eduardo A F Coelho

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