Mapping IgA Epitope and Cross-Reactivity between Severe Acute Respiratory Syndrome-Associated Coronavirus 2 and DENV

Background: The newly introduced COVID-19 vaccines have reduced disease severity and hospitalizations. However, they do not significantly prevent infection or transmission. In the same context, measuring IgM and IgG antibody levels is important, but it does not provide information about the status o...

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Main Authors: Salvatore G. De-Simone, Paloma Napoleão-Pêgo, Guilherme C. Lechuga, João P. R. S. Carvalho, Maria E. Monteiro, Carlos M. Morel, David W. Provance
Format: Article
Language:English
Published: MDPI AG 2023-11-01
Series:Vaccines
Subjects:
Online Access:https://www.mdpi.com/2076-393X/11/12/1749
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author Salvatore G. De-Simone
Paloma Napoleão-Pêgo
Guilherme C. Lechuga
João P. R. S. Carvalho
Maria E. Monteiro
Carlos M. Morel
David W. Provance
author_facet Salvatore G. De-Simone
Paloma Napoleão-Pêgo
Guilherme C. Lechuga
João P. R. S. Carvalho
Maria E. Monteiro
Carlos M. Morel
David W. Provance
author_sort Salvatore G. De-Simone
collection DOAJ
description Background: The newly introduced COVID-19 vaccines have reduced disease severity and hospitalizations. However, they do not significantly prevent infection or transmission. In the same context, measuring IgM and IgG antibody levels is important, but it does not provide information about the status of the mucosal immune response. This article describes a comprehensive mapping of IgA epitopes of the S protein, its cross-reactivity, and the development of an ELISA-peptide assay. Methods: IgA epitope mapping was conducted using SPOT synthesis and sera from RT-qPCR COVID-19-positive patients. Specific and cross-reacting epitopes were identified, and an evolutionary analysis from the early Wuhan strain to the Omicron variant was performed using bioinformatics tools and a microarray of peptides. The selected epitopes were chemically synthesized and evaluated using ELISA-IgA. Results: A total of 40 IgA epitopes were identified with 23 in S1 and 17 in the S2 subunit. Among these, at least 23 epitopes showed cross-reactivity with DENV and other organisms and 24 showed cross-reactivity with other associated coronaviruses. Three MAP4 polypeptides were validated by ELISA, demonstrating a sensitivity of 90–99.96% and a specificity of 100%. Among the six IgA-RBD epitopes, only the SC/18 epitope of the Omicron variants (BA.2 and BA.2.12.1) presented a single IgA epitope. Conclusions: This research unveiled the IgA epitome of the S protein and identified many epitopes that exhibit cross-reactivity with DENV and other coronaviruses. The S protein of variants from Wuhan to Omicron retains many conserved IgA epitopes except for one epitope (#SCov/18). The cross-reactivity with DENV suggests limitations in using the whole S protein or the S1/S2/RBD segment for IgA serological diagnostic tests for COVID-19. The expression of these identified specific epitopes as diagnostic biomarkers could facilitate monitoring mucosal immunity to COVID-19, potentially leading to more accurate diagnoses and alternative mucosal vaccines.
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spelling doaj.art-8a92fc733da64c1497a5cd69f94b9a5c2023-12-22T14:46:54ZengMDPI AGVaccines2076-393X2023-11-011112174910.3390/vaccines11121749Mapping IgA Epitope and Cross-Reactivity between Severe Acute Respiratory Syndrome-Associated Coronavirus 2 and DENVSalvatore G. De-Simone0Paloma Napoleão-Pêgo1Guilherme C. Lechuga2João P. R. S. Carvalho3Maria E. Monteiro4Carlos M. Morel5David W. Provance6Center for Technological Development in Health (CDTS)/National Institute of Science and Technology for Innovation in Neglected Population Diseases (INCT-IDPN), Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, RJ, BrazilCenter for Technological Development in Health (CDTS)/National Institute of Science and Technology for Innovation in Neglected Population Diseases (INCT-IDPN), Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, RJ, BrazilCenter for Technological Development in Health (CDTS)/National Institute of Science and Technology for Innovation in Neglected Population Diseases (INCT-IDPN), Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, RJ, BrazilCenter for Technological Development in Health (CDTS)/National Institute of Science and Technology for Innovation in Neglected Population Diseases (INCT-IDPN), Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, RJ, BrazilCenter for Technological Development in Health (CDTS)/National Institute of Science and Technology for Innovation in Neglected Population Diseases (INCT-IDPN), Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, RJ, BrazilCenter for Technological Development in Health (CDTS)/National Institute of Science and Technology for Innovation in Neglected Population Diseases (INCT-IDPN), Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, RJ, BrazilCenter for Technological Development in Health (CDTS)/National Institute of Science and Technology for Innovation in Neglected Population Diseases (INCT-IDPN), Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, RJ, BrazilBackground: The newly introduced COVID-19 vaccines have reduced disease severity and hospitalizations. However, they do not significantly prevent infection or transmission. In the same context, measuring IgM and IgG antibody levels is important, but it does not provide information about the status of the mucosal immune response. This article describes a comprehensive mapping of IgA epitopes of the S protein, its cross-reactivity, and the development of an ELISA-peptide assay. Methods: IgA epitope mapping was conducted using SPOT synthesis and sera from RT-qPCR COVID-19-positive patients. Specific and cross-reacting epitopes were identified, and an evolutionary analysis from the early Wuhan strain to the Omicron variant was performed using bioinformatics tools and a microarray of peptides. The selected epitopes were chemically synthesized and evaluated using ELISA-IgA. Results: A total of 40 IgA epitopes were identified with 23 in S1 and 17 in the S2 subunit. Among these, at least 23 epitopes showed cross-reactivity with DENV and other organisms and 24 showed cross-reactivity with other associated coronaviruses. Three MAP4 polypeptides were validated by ELISA, demonstrating a sensitivity of 90–99.96% and a specificity of 100%. Among the six IgA-RBD epitopes, only the SC/18 epitope of the Omicron variants (BA.2 and BA.2.12.1) presented a single IgA epitope. Conclusions: This research unveiled the IgA epitome of the S protein and identified many epitopes that exhibit cross-reactivity with DENV and other coronaviruses. The S protein of variants from Wuhan to Omicron retains many conserved IgA epitopes except for one epitope (#SCov/18). The cross-reactivity with DENV suggests limitations in using the whole S protein or the S1/S2/RBD segment for IgA serological diagnostic tests for COVID-19. The expression of these identified specific epitopes as diagnostic biomarkers could facilitate monitoring mucosal immunity to COVID-19, potentially leading to more accurate diagnoses and alternative mucosal vaccines.https://www.mdpi.com/2076-393X/11/12/1749COVID-19SARS-CoV-2SARS-CoV-2 variantsIgA epitopesIgA-diagnosticcross-reactive epitopes
spellingShingle Salvatore G. De-Simone
Paloma Napoleão-Pêgo
Guilherme C. Lechuga
João P. R. S. Carvalho
Maria E. Monteiro
Carlos M. Morel
David W. Provance
Mapping IgA Epitope and Cross-Reactivity between Severe Acute Respiratory Syndrome-Associated Coronavirus 2 and DENV
Vaccines
COVID-19
SARS-CoV-2
SARS-CoV-2 variants
IgA epitopes
IgA-diagnostic
cross-reactive epitopes
title Mapping IgA Epitope and Cross-Reactivity between Severe Acute Respiratory Syndrome-Associated Coronavirus 2 and DENV
title_full Mapping IgA Epitope and Cross-Reactivity between Severe Acute Respiratory Syndrome-Associated Coronavirus 2 and DENV
title_fullStr Mapping IgA Epitope and Cross-Reactivity between Severe Acute Respiratory Syndrome-Associated Coronavirus 2 and DENV
title_full_unstemmed Mapping IgA Epitope and Cross-Reactivity between Severe Acute Respiratory Syndrome-Associated Coronavirus 2 and DENV
title_short Mapping IgA Epitope and Cross-Reactivity between Severe Acute Respiratory Syndrome-Associated Coronavirus 2 and DENV
title_sort mapping iga epitope and cross reactivity between severe acute respiratory syndrome associated coronavirus 2 and denv
topic COVID-19
SARS-CoV-2
SARS-CoV-2 variants
IgA epitopes
IgA-diagnostic
cross-reactive epitopes
url https://www.mdpi.com/2076-393X/11/12/1749
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