Comprehensive Analysis of the Immune Response to SARS-CoV-2 Epitopes: Unveiling Potential Targets for Vaccine Development

SARS-CoV-2 continues to be a major global health threat. In this study, we performed a comprehensive meta-analysis on the epitopes of SARS-CoV-2, revealing its immunological landscape. Furthermore, using Shannon entropy for sequence conservation analysis and structural network-based methods identifi...

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Main Authors: Huixiong Deng, Yanlei Li, Gefei Wang, Rui Li
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Biology
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Online Access:https://www.mdpi.com/2079-7737/14/1/67
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author Huixiong Deng
Yanlei Li
Gefei Wang
Rui Li
author_facet Huixiong Deng
Yanlei Li
Gefei Wang
Rui Li
author_sort Huixiong Deng
collection DOAJ
description SARS-CoV-2 continues to be a major global health threat. In this study, we performed a comprehensive meta-analysis on the epitopes of SARS-CoV-2, revealing its immunological landscape. Furthermore, using Shannon entropy for sequence conservation analysis and structural network-based methods identified candidate epitopes that are highly conserved and evolutionarily constrained in SARS-CoV-2 and other zoonotic coronaviruses. Finally, the population coverage of T cell epitopes was analyzed. The results highlighted regions within each SARS-CoV-2 protein where the immunological activity of antibodies, CD4<sup>+</sup>, and CD8<sup>+</sup> T cell responses was predominantly concentrated. Sequence-based correlation analysis found that epitopes recognized by B cells and CD4<sup>+</sup> T cells showed a positive correlation with high viral variability, and these high variability regions were typically linked to robust immune responses. Conversely, epitopes recognized by CD8<sup>+</sup> T cells exhibited a negative correlation with high variability. From a structural network degree perspective, no clear correlation was identified between B cell antibody epitopes and CD4<sup>+</sup> T cell reactivity with the degree of residue network connectivity. However, a significant positive correlation was observed between CD8<sup>+</sup> T cell reactivity and the degree of residue network connectivity. By integrating sequence Shannon entropy and structural network correlation analysis, we pinpointed highly conserved and evolutionarily constrained SARS-CoV-2 candidate epitopes. Furthermore, we utilized immunoinformatics to assess the conservation of SARS-CoV-2 within coronaviruses and the population coverage of these epitopes. Our analysis uncovered key immune responses linked to preventing viral infection and viral clearance, emphasized areas of interest for broad-spectrum SARS-CoV-2 vaccine development, and offered insights for future research and clinical applications.
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spelling doaj-art-c580439001524786b1d1e5fd231dce4e2025-01-24T13:23:30ZengMDPI AGBiology2079-77372025-01-011416710.3390/biology14010067Comprehensive Analysis of the Immune Response to SARS-CoV-2 Epitopes: Unveiling Potential Targets for Vaccine DevelopmentHuixiong Deng0Yanlei Li1Gefei Wang2Rui Li3Chaoshan Branch of State Key Laboratory for Esophageal Cancer Prevention and Treatment, Shantou University Medical College, Shantou 515041, ChinaChaoshan Branch of State Key Laboratory for Esophageal Cancer Prevention and Treatment, Shantou University Medical College, Shantou 515041, ChinaChaoshan Branch of State Key Laboratory for Esophageal Cancer Prevention and Treatment, Shantou University Medical College, Shantou 515041, ChinaChaoshan Branch of State Key Laboratory for Esophageal Cancer Prevention and Treatment, Shantou University Medical College, Shantou 515041, ChinaSARS-CoV-2 continues to be a major global health threat. In this study, we performed a comprehensive meta-analysis on the epitopes of SARS-CoV-2, revealing its immunological landscape. Furthermore, using Shannon entropy for sequence conservation analysis and structural network-based methods identified candidate epitopes that are highly conserved and evolutionarily constrained in SARS-CoV-2 and other zoonotic coronaviruses. Finally, the population coverage of T cell epitopes was analyzed. The results highlighted regions within each SARS-CoV-2 protein where the immunological activity of antibodies, CD4<sup>+</sup>, and CD8<sup>+</sup> T cell responses was predominantly concentrated. Sequence-based correlation analysis found that epitopes recognized by B cells and CD4<sup>+</sup> T cells showed a positive correlation with high viral variability, and these high variability regions were typically linked to robust immune responses. Conversely, epitopes recognized by CD8<sup>+</sup> T cells exhibited a negative correlation with high variability. From a structural network degree perspective, no clear correlation was identified between B cell antibody epitopes and CD4<sup>+</sup> T cell reactivity with the degree of residue network connectivity. However, a significant positive correlation was observed between CD8<sup>+</sup> T cell reactivity and the degree of residue network connectivity. By integrating sequence Shannon entropy and structural network correlation analysis, we pinpointed highly conserved and evolutionarily constrained SARS-CoV-2 candidate epitopes. Furthermore, we utilized immunoinformatics to assess the conservation of SARS-CoV-2 within coronaviruses and the population coverage of these epitopes. Our analysis uncovered key immune responses linked to preventing viral infection and viral clearance, emphasized areas of interest for broad-spectrum SARS-CoV-2 vaccine development, and offered insights for future research and clinical applications.https://www.mdpi.com/2079-7737/14/1/67SARS-CoV-2epitopestructure-based networkimmune landscapebroad-spectrum
spellingShingle Huixiong Deng
Yanlei Li
Gefei Wang
Rui Li
Comprehensive Analysis of the Immune Response to SARS-CoV-2 Epitopes: Unveiling Potential Targets for Vaccine Development
Biology
SARS-CoV-2
epitope
structure-based network
immune landscape
broad-spectrum
title Comprehensive Analysis of the Immune Response to SARS-CoV-2 Epitopes: Unveiling Potential Targets for Vaccine Development
title_full Comprehensive Analysis of the Immune Response to SARS-CoV-2 Epitopes: Unveiling Potential Targets for Vaccine Development
title_fullStr Comprehensive Analysis of the Immune Response to SARS-CoV-2 Epitopes: Unveiling Potential Targets for Vaccine Development
title_full_unstemmed Comprehensive Analysis of the Immune Response to SARS-CoV-2 Epitopes: Unveiling Potential Targets for Vaccine Development
title_short Comprehensive Analysis of the Immune Response to SARS-CoV-2 Epitopes: Unveiling Potential Targets for Vaccine Development
title_sort comprehensive analysis of the immune response to sars cov 2 epitopes unveiling potential targets for vaccine development
topic SARS-CoV-2
epitope
structure-based network
immune landscape
broad-spectrum
url https://www.mdpi.com/2079-7737/14/1/67
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AT yanleili comprehensiveanalysisoftheimmuneresponsetosarscov2epitopesunveilingpotentialtargetsforvaccinedevelopment
AT gefeiwang comprehensiveanalysisoftheimmuneresponsetosarscov2epitopesunveilingpotentialtargetsforvaccinedevelopment
AT ruili comprehensiveanalysisoftheimmuneresponsetosarscov2epitopesunveilingpotentialtargetsforvaccinedevelopment