{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T06:22:22Z","timestamp":1783578142874,"version":"3.55.0"},"reference-count":35,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T00:00:00Z","timestamp":1736812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural Science Foundation of Guangdong Province","award":["2021A1515012470"],"award-info":[{"award-number":["2021A1515012470"]}]},{"name":"Natural Science Foundation of Guangdong Province","award":["2022A1515010540"],"award-info":[{"award-number":["2022A1515010540"]}]},{"name":"Natural Science Foundation of Guangdong Province","award":["2020LKSFG01E"],"award-info":[{"award-number":["2020LKSFG01E"]}]},{"name":"Natural Science Foundation of Guangdong Province","award":["Shanfuke (2021)88-STKJ2021197"],"award-info":[{"award-number":["Shanfuke (2021)88-STKJ2021197"]}]},{"name":"Natural Science Foundation of Guangdong Province","award":["Shanfuke (2020)53-51"],"award-info":[{"award-number":["Shanfuke (2020)53-51"]}]},{"name":"2020 Li Ka Shing Foundation Cross-Disciplinary Research Grant","award":["2021A1515012470"],"award-info":[{"award-number":["2021A1515012470"]}]},{"name":"2020 Li Ka Shing Foundation Cross-Disciplinary Research Grant","award":["2022A1515010540"],"award-info":[{"award-number":["2022A1515010540"]}]},{"name":"2020 Li Ka Shing Foundation Cross-Disciplinary Research Grant","award":["2020LKSFG01E"],"award-info":[{"award-number":["2020LKSFG01E"]}]},{"name":"2020 Li Ka Shing Foundation Cross-Disciplinary Research Grant","award":["Shanfuke (2021)88-STKJ2021197"],"award-info":[{"award-number":["Shanfuke (2021)88-STKJ2021197"]}]},{"name":"2020 Li Ka Shing Foundation Cross-Disciplinary Research Grant","award":["Shanfuke (2020)53-51"],"award-info":[{"award-number":["Shanfuke (2020)53-51"]}]},{"name":"Shantou Science and Technology Bureau","award":["2021A1515012470"],"award-info":[{"award-number":["2021A1515012470"]}]},{"name":"Shantou Science and Technology Bureau","award":["2022A1515010540"],"award-info":[{"award-number":["2022A1515010540"]}]},{"name":"Shantou Science and Technology Bureau","award":["2020LKSFG01E"],"award-info":[{"award-number":["2020LKSFG01E"]}]},{"name":"Shantou Science and Technology Bureau","award":["Shanfuke (2021)88-STKJ2021197"],"award-info":[{"award-number":["Shanfuke (2021)88-STKJ2021197"]}]},{"name":"Shantou Science and Technology Bureau","award":["Shanfuke (2020)53-51"],"award-info":[{"award-number":["Shanfuke (2020)53-51"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>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+, and CD8+ T cell responses was predominantly concentrated. Sequence-based correlation analysis found that epitopes recognized by B cells and CD4+ 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+ 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+ T cell reactivity with the degree of residue network connectivity. However, a significant positive correlation was observed between CD8+ 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.<\/jats:p>","DOI":"10.3390\/biology14010067","type":"journal-article","created":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T07:35:47Z","timestamp":1736840147000},"page":"67","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Comprehensive Analysis of the Immune Response to SARS-CoV-2 Epitopes: Unveiling Potential Targets for Vaccine Development"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-8752-7822","authenticated-orcid":false,"given":"Huixiong","family":"Deng","sequence":"first","affiliation":[{"name":"Chaoshan Branch of State Key Laboratory for Esophageal Cancer Prevention and Treatment, Shantou University Medical College, Shantou 515041, China"},{"name":"Center of Pathogen Biology and Immunology, Shantou University Medical College, Shantou 515041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanlei","family":"Li","sequence":"additional","affiliation":[{"name":"Chaoshan Branch of State Key Laboratory for Esophageal Cancer Prevention and Treatment, Shantou University Medical College, Shantou 515041, China"},{"name":"Center of Pathogen Biology and Immunology, Shantou University Medical College, Shantou 515041, China"},{"name":"Nursing Research Center, Shantou University Medical College, Shantou 515041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3070-3586","authenticated-orcid":false,"given":"Gefei","family":"Wang","sequence":"additional","affiliation":[{"name":"Chaoshan Branch of State Key Laboratory for Esophageal Cancer Prevention and Treatment, Shantou University Medical College, Shantou 515041, China"},{"name":"Center of Pathogen Biology and Immunology, Shantou University Medical College, Shantou 515041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Li","sequence":"additional","affiliation":[{"name":"Chaoshan Branch of State Key Laboratory for Esophageal Cancer Prevention and Treatment, Shantou University Medical College, Shantou 515041, China"},{"name":"Center of Pathogen Biology and Immunology, Shantou University Medical College, Shantou 515041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1038\/s41422-024-01000-8","article-title":"Deletion of V483 in the spike confers evolutionary advantage on SARS-CoV-2 for human adaptation and host-range expansion after a prolonged pandemic","volume":"34","author":"Yue","year":"2024","journal-title":"Cell Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e70","DOI":"10.1016\/S1473-3099(23)00744-2","article-title":"Fast evolution of SARS-CoV-2 BA.2.86 to JN.1 under heavy immune pressure","volume":"24","author":"Yang","year":"2024","journal-title":"Lancet Infect. 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