{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T06:07:49Z","timestamp":1788847669083,"version":"build-2803163510"},"reference-count":80,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to the COVID-19 pandemic, which resulted in millions of deaths globally and had profound social, economic, and political consequences. Although effective vaccines and antiviral therapies have substantially reduced the global burden of COVID-19, the continued emergence of viral variants highlights the need for next-generation effective vaccine strategies capable of providing broader and more durable immune response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this work, we provide an immunoinformatic approach for multi-epitope vaccine (MEV) design and prediction. Based on the spike (S) and nucleocapsid (N) proteins of SARS-CoV-2, immunoinformatic methods were used to identify the epitopes for B cells, cytotoxic T lymphocytes (CTL), and helper T lymphocytes (HTL). The B cell, CTL, and HTL epitopes were conjugated with flexible linkers GSG, GSGG, and a Gb-1 peptide conjugated to the C-terminal of the MEV ccandidate.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The final MEV candidate exhibited favorable predicted characteristics, with a molecular weight of approximately 55.47 kDa and a length of 498 amino acid residues. Computational analyses indicated that the designed construct was antigenic, non-toxic, non-allergenic, and possessed suitable physicochemical properties and predicted solubility, supporting its potential as a vaccine candidate for further investigation. Molecular docking analysis demonstrated favorable interactions between the MEV construct and selected Toll-like receptors (TLRs), while molecular dynamics (MD) simulations suggested the stability of the vaccine-receptor complexes throughout the simulation period. Furthermore, C-ImmSim-based immune simulation predicted the induction of both humoral and cellular immune responses following the proposed immunization schedule. Collectively, these findings highlight the potential of the designed MEV construct as a computationally optimized vaccine candidate and provide a framework for future experimental evaluation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This study presents a computationally designed MEV candidate against SARS-CoV-2 by integrating immunoinformatics approaches, structural modeling, molecular docking, molecular dynamics simulations, and immune response prediction. The findings suggest that the proposed MEV construct may possess favorable immunogenic and structural properties; however, experimental validation through\n                      <jats:italic>in vitro<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      studies remains essential to confirm its safety, immunogenicity, and protective efficacy. The proposed approach provides a valuable strategy for accelerating rational vaccine design and may serve as a foundation for future development of experimentally validated vaccine candidates.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1906485","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T05:35:30Z","timestamp":1788845730000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Multi-epitope vaccine targeting SARS-CoV-2 omicron S and N proteins promotes enhanced immunity: a computational approach"],"prefix":"10.3389","volume":"17","author":[{"given":"Xinyi","family":"Xu","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Immunology, State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arslan","family":"Habib","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]},{"name":"Shanghai Key Laboratory of Biliary Tract Disease Research","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naishuo","family":"Zhu","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University","place":["Shanghai, China"]},{"name":"Yaoyanda Technology Development Co., Ltd.","place":["Suzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jfma.2024.08.021","article-title":"Worldwide SARS-CoV-2 Omicron variant infection: Emerging sub-variants and future vaccination perspectives","volume":"124","author":"Kung","year":"2025","journal-title":"J Formos Med Assoc"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2025.55442","article-title":"Global assessment of COVID-19 mortality displacement from 2020 to 2024","volume":"9","author":"Chen","year":"2026","journal-title":"JAMA Netw Open"},{"key":"B3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-1-4939-9544-8_68-2","article-title":"Coronaviruses: pandemic SARS-coV-2","volume-title":"Viral Infections of Humans: Epidemiology and Control","author":"Cowling","year":"2026"},{"key":"B4","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/B978-0-323-95650-5.00035-5","article-title":"Chapter 1 - the Historical Aspects of the Sars-Cov-2 Virus and the Ensuing Pandemic","volume-title":"Linking Neuroscience and Behavior in Covid-19","author":"Nasrin","year":"2024"},{"key":"B5","first-page":"1","article-title":"Chapter 1 - Coronavirus (SARS-coV-2)","volume-title":"Deadly Rna Viruses","author":"Raj","year":"2026"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(20)30251-8","article-title":"Genomic characterisation and epidemiology of 2019 novel coronavirus: Implications for virus origins and receptor binding","volume":"395","author":"Lu","year":"2020","journal-title":"Lancet"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2008-3","article-title":"A new coronavirus associated with human respiratory disease in China","volume":"579","author":"Wu","year":"2020","journal-title":"Nature"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-025-01185-8","article-title":"SARS-CoV-2 spike protein: Structure, viral entry and variants","volume":"23","author":"Chen","year":"2025","journal-title":"Nat Rev Microbiol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/j.cell.2020.02.058","article-title":"Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein","volume":"181","author":"Walls","year":"2020","journal-title":"Cell"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.77.16.8801-8811.2003","article-title":"The coronavirus spike protein is a class I virus fusion protein: Structural and functional characterization of the fusion core complex","volume":"77","author":"Bosch","year":"2003","journal-title":"J Virol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1007\/s00705-025-06327-0","article-title":"ACE2, a therapeutic target of COVID-19, needs to be treated with caution","volume":"170","author":"Liu","year":"2025","journal-title":"Arch Virol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2020.09.002","article-title":"Is toll-like receptor 4 involved in the severity of COVID-19 pathology in patients with cardiometabolic comorbidities","volume":"58","author":"Brand\u00e3o","year":"2021","journal-title":"Cytokine Growth Factor Rev"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines13040406","article-title":"Next-generation adenoviral vector-based vaccines for severe acute respiratory syndrome coronavirus-2","volume":"13","author":"Murala","year":"2025","journal-title":"Vaccines"},{"key":"B14","doi-asserted-by":"publisher","first-page":"2991","DOI":"10.3390\/v6082991","article-title":"The coronavirus nucleocapsid is a multifunctional protein","volume":"6","author":"McBride","year":"2014","journal-title":"Viruses"},{"key":"B15","doi-asserted-by":"publisher","first-page":"10.1128\/jvi.00647-20","DOI":"10.1128\/jvi.00647-20","article-title":"The nucleocapsid protein of SARS-CoV-2: A target for vaccine development","volume":"94","author":"Dutta","year":"2020","journal-title":"J Virol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abp9770","article-title":"Cell surface SARS-CoV-2 nucleocapsid protein modulates innate and adaptive immunity","volume":"8","author":"L\u00f3pez-Mu\u00f1oz","year":"2022","journal-title":"Sci Adv"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abq1945","article-title":"Dual spike and nucleocapsid mRNA vaccination confer protection against SARS-CoV-2 Omicron and Delta variants in preclinical models","volume":"14","author":"Hajnik","year":"2022","journal-title":"Sci Transl Med"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1188605","article-title":"OVX033, a nucleocapsid-based vaccine candidate, provides broad-spectrum protection against SARS-CoV-2 variants in a hamster challenge model","volume":"14","author":"Primard","year":"2023","journal-title":"Front Immunol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109664","article-title":"Combining spike- and nucleocapsid-based vaccines improves distal control of SARS-CoV-2","volume":"36","author":"Dangi","year":"2021","journal-title":"Cell Rep"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.9.6337","article-title":"Prior immunization with severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) nucleocapsid protein causes severe pneumonia in mice infected with SARS-CoV","volume":"181","author":"Yasui","year":"2008","journal-title":"J Immunol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2104241118","article-title":"Ongoing global and regional adaptive evolution of SARS-CoV-2","volume":"118","author":"Rochman","year":"2021","journal-title":"Proc Natl Acad Sci USA"},{"key":"B22","article-title":"Advances in computational vaccinology: From antigen discovery to immune simulation","volume":"15","author":"Yu","year":"2025","journal-title":"Comput Mol Biol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2025.e41714","article-title":"Computational epitope-based vaccine design with bioinformatics approach; a review","volume":"11","author":"Basmenj","year":"2025","journal-title":"Heliyon"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1080\/08830185.2019.1657426","article-title":"Immunoinformatics: In silico approaches and computational design of a multi-epitope, immunogenic protein","volume":"38","author":"Bahrami","year":"2019","journal-title":"Int Rev Immunol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3409","article-title":"Key roles of adjuvants in modern vaccines","volume":"19","author":"Reed","year":"2013","journal-title":"Nat Med"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00298","article-title":"Antibody specific B-cell epitope predictions: Leveraging information from antibody-antigen protein complexes","volume":"10","author":"Jespersen","year":"2019","journal-title":"Front Immunol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"2464","DOI":"10.1038\/s41598-024-53028-w","article-title":"Prediction of linear B-cell epitopes based on protein sequence features and BERT embeddings","volume":"14","author":"Liu","year":"2024","journal-title":"Sci Rep"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-11-479","article-title":"Computational analysis and modeling of cleavage by the immunoproteasome and the constitutive proteasome","volume":"11","author":"Diez-Rivero","year":"2010","journal-title":"BMC Bioinf"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1186\/1745-6150-8-30","article-title":"Designing of interferon-gamma inducing MHC class-II binders","volume":"8","author":"Dhanda","year":"2013","journal-title":"Biol Direct"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-8-4","article-title":"VaxiJen: A server for prediction of protective antigens, tumour antigens and subunit vaccines","volume":"8","author":"Doytchinova","year":"2007","journal-title":"BMC Bioinf"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq551","article-title":"High-throughput prediction of protein antigenicity using protein microarray data","volume":"26","author":"Magnan","year":"2010","journal-title":"Bioinformatics"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt619","article-title":"AllergenFP: Allergenicity prediction by descriptor fingerprints","volume":"30","author":"Dimitrov","year":"2014","journal-title":"Bioinformatics"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz452","article-title":"IEDB-AR: immune epitope database-analysis resource in 2019","volume":"47","author":"Dhanda","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.6026\/97320630012074","article-title":"MFPPI - multi FASTA protparam interface","volume":"12","author":"Garg","year":"2016","journal-title":"Bioinformation"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0073957","article-title":"In silico approach for predicting toxicity of peptides and proteins","volume":"8","author":"Gupta","year":"2013","journal-title":"PloS One"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1007\/s00251-013-0714-9","article-title":"MHCcluster, a method for functional clustering of MHC molecules","volume":"65","author":"Thomsen","year":"2013","journal-title":"Immunogenetics"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1177\/2472555217690483","article-title":"Phage display-derived ligand for mucosal transcytotic receptor GP-2 promotes antigen delivery to M cells and induces antigen-specific immune response","volume":"22","author":"Khan","year":"2017","journal-title":"SLAS Discov"},{"key":"B38","doi-asserted-by":"publisher","first-page":"2432","DOI":"10.3390\/ijms25042432","article-title":"Immunoinformatic identification of multiple epitopes of GP120 protein of HIV-1 to enhance the immune response against HIV-1 infection","volume":"25","author":"Habib","year":"2024","journal-title":"Int J Mol Sci"},{"key":"B39","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1007\/978-1-0716-1884-4_2","article-title":"Principles in immunology for the design and development of vaccines","volume":"2410","author":"Meyer","year":"2022","journal-title":"Methods Mol Biol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz297","article-title":"The PSIPRED protein analysis workbench: 20 years on","volume":"47","author":"Buchan","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1126\/science.abj8754","article-title":"Accurate prediction of protein structures and interactions using a three-track neural network","volume":"373","author":"Baek","year":"2021","journal-title":"Science"},{"key":"B42","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1002\/prot.24377","article-title":"Evaluation of predictions in the CASP10 model refinement category","author":"Nugent","year":"2014","journal-title":"Proteins"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1002\/prot.20530","article-title":"Main-chain conformational tendencies of amino acids","volume":"60","author":"Anderson","year":"2005","journal-title":"Proteins"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkm290","article-title":"ProSA-web: Interactive web service for the recognition of errors in three-dimensional structures of proteins","volume":"35","author":"Wiederstein","year":"2007","journal-title":"Nucleic Acids Res"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btg231","article-title":"Disulfide by Design: A computational method for the rational design of disulfide bonds in proteins","volume":"19","author":"Dombkowski","year":"2003","journal-title":"Bioinformatics"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2016.169","article-title":"The ClusPro web server for protein-protein docking","volume":"12","author":"Kozakov","year":"2017","journal-title":"Nat Protoc"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1002\/pro.3289","article-title":"PDBsum: Structural summaries of PDB entries","volume":"27","author":"Laskowski","year":"2018","journal-title":"Protein Sci"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku339","article-title":"iMODS: Internal coordinates normal mode analysis server","volume":"42","author":"L\u00f3pez-Blanco","year":"2014","journal-title":"Nucleic Acids Res"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/842329","article-title":"How the interval between prime and boost injection affects the immune response in a computational model of the immune system","volume":"2012","author":"Castiglione","year":"2012","journal-title":"Comput Math Methods Med"},{"key":"B50","doi-asserted-by":"publisher","first-page":"9044","DOI":"10.1038\/s41598-018-26689-7","article-title":"Subtractive proteomics to identify novel drug targets and reverse vaccinology for the development of chimeric vaccine against Acinetobacter baumannii","volume":"8","author":"Solanki","year":"2018","journal-title":"Sci Rep"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.883010","article-title":"The expanding arsenal of cytotoxic T cells","volume":"13","author":"Cassioli","year":"2022","journal-title":"Front Immunol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.202000047","article-title":"Learning from the past: Possible urgent prevention and treatment options for severe acute respiratory infections caused by 2019-ncov","volume":"21","author":"Morse","year":"2020","journal-title":"ChemBioChem"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2018.1548977","article-title":"Design of novel multi-epitope vaccines against severe acute respiratory syndrome validated through multistage molecular interaction and dynamics","volume":"37","author":"Srivastava","year":"2019","journal-title":"J Biomol Struct Dyn"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1038\/cmi.2017.92","article-title":"Multi-epitope vaccines: A promising strategy against tumors and viral infections","volume":"15","author":"Zhang","year":"2018","journal-title":"Cell Mol Immunol"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro.2016.81","article-title":"Sars and mers: Recent insights into emerging coronaviruses","volume":"14","author":"de Wit","year":"2016","journal-title":"Nat Rev Microbiol"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines13020149","article-title":"Design and immune profile of multi-epitope synthetic antigen vaccine against sars-cov-2: An in silico and in vivo approach","volume":"13","author":"Inven\u00e7\u00e3o","year":"2025","journal-title":"Vaccines"},{"key":"B57","doi-asserted-by":"publisher","first-page":"2517","DOI":"10.1038\/s41598-019-39299-8","article-title":"Designing a multi-epitope based vaccine to combat kaposi sarcoma utilizing immunoinformatics approach","volume":"9","author":"Chauhan","year":"2019","journal-title":"Sci Rep"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2019.1707120","article-title":"Multi-epitope based vaccine against yellow fever virus applying immunoinformatics approaches","volume":"39","author":"Tosta","year":"2021","journal-title":"J Biomol Struct Dyn"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.14686","article-title":"A novel multi-epitope vaccine from mmsa-1 and dkk1 for multiple myeloma immunotherapy","volume":"178","author":"Lu","year":"2017","journal-title":"Br J Haematol"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-013-1516-5","article-title":"Immunologic response to the survivin-derived multi-epitope vaccine emd640744 in patients with advanced solid tumors","volume":"63","author":"Lennerz","year":"2014","journal-title":"Cancer Immunol Immunother"},{"key":"B61","doi-asserted-by":"publisher","first-page":"9828","DOI":"10.3390\/ijms26199828","article-title":"Immunoinformatic prediction of hiv-1 glycoprotein gp120 and nef epitopes conjugated to hbsag-binding protein (sbp) to induce the humoral and cellular immune response","volume":"26","author":"Habib","year":"2025","journal-title":"Int J Mol Sci"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.24079\/cajms.2017.06.014","article-title":"Molecular biology of the cell, sixth edition","volume":"3","author":"Jamiyansuren","year":"2017","journal-title":"Cent Asian J Med Sci"},{"key":"B63","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.imlet.2019.12.002","article-title":"Role of allograft inflammatory factor-1 in pathogenesis of diseases","volume":"218","author":"Sikora","year":"2020","journal-title":"Immunol Lett"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e35129","article-title":"Bioinformatic elucidation of conserved epitopes to design a potential vaccine candidate against existing and emerging sars-cov-2 variants of concern","volume":"10","author":"Rastogi","year":"2024","journal-title":"Heliyon"},{"key":"B65","doi-asserted-by":"publisher","first-page":"9562","DOI":"10.1038\/s41598-025-92956-z","article-title":"Computationally designed multi-epitope vaccine construct targeting the sars-cov-2 spike protein elicits robust immune responses in silico","volume":"15","author":"Deepthi","year":"2025","journal-title":"Sci Rep"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2021.1883111","article-title":"Exploring the cancer-testis antigen boris to design a novel multi-epitope vaccine against breast cancer based on immunoinformatics approaches","volume":"40","author":"Mahdevar","year":"2022","journal-title":"J Biomol Struct Dyn"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2020.10.016","article-title":"Exploring the out of sight antigens of sars-cov-2 to design a candidate multi-epitope vaccine by utilizing immunoinformatics approaches","volume":"38","author":"Safavi","year":"2020","journal-title":"Vaccine"},{"key":"B68","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1080\/07391102.2020.1792347","article-title":"Designing a multi-epitope vaccine against sars-cov-2: An immunoinformatics approach","volume":"40","author":"Samad","year":"2022","journal-title":"J Biomol Struct Dyn"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1515\/jib-2024-0025","article-title":"Immunoinformatics-guided design of a multiepitope peptide vaccine targeting the receptor-binding domain of sars-cov-2 spike glycoprotein: Insights from Indonesian samples","volume":"22","author":"Faizal","year":"2025","journal-title":"J Integr Bioinform"},{"key":"B70","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.1016\/j.cell.2020.04.035","article-title":"Sars-cov-2 receptor ace2 is an interferon-stimulated gene in human airway epithelial cells and is detected in specific cell subsets across tissues","volume":"181","author":"Ziegler","year":"2020","journal-title":"Cell"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00638-15","article-title":"Toll-like receptor 3 signaling via trif contributes to a protective innate immune response to severe acute respiratory syndrome coronavirus infection","volume":"6","author":"Totura","year":"2015","journal-title":"mBio"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1089\/vim.2011.0099","article-title":"Sars-cov regulates immune function-related gene expression in human monocytic cells","volume":"25","author":"Hu","year":"2012","journal-title":"Viral Immunol"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2021.628585","article-title":"Prospective role of peptide-based antiviral therapy against the main protease of sars-cov-2","volume":"8","author":"Mahmud","year":"2021","journal-title":"Front Mol Biosci"},{"key":"B74","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1186\/s12879-025-11066-3","article-title":"Designing a multi-epitope universal vaccine for concurrent infections of sars-cov-2 and influenza viruses using an immunoinformatics approach","volume":"25","author":"Mohammadipour","year":"2025","journal-title":"BMC Infect Dis"},{"key":"B75","doi-asserted-by":"publisher","first-page":"17617","DOI":"10.1038\/s41598-020-74091-z","article-title":"Codon optimization with deep learning to enhance protein expression","volume":"10","author":"Fu","year":"2020","journal-title":"Sci Rep"},{"key":"B76","first-page":"15","article-title":"Recombinant protein production in escherichia coli: Optimization strategies","volume":"9","author":"Mohite","year":"2026","journal-title":"Vasc Endovascular Rev"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0334662","article-title":"Designing a novel vaccine against covid-19 based on spike sars-cov-2 notable mutations using immunoinformatics approaches","volume":"21","author":"Rahimnahal","year":"2026","journal-title":"PloS One"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.34172\/ajcmi.3692","article-title":"Harnessing the power of bioinformatics pipelines to develop an anti-sars-cov-2 pan-species vaccine: A post-pandemic description","volume":"12","author":"Roayaei Ardakani","year":"2025","journal-title":"Avicenna J Clin Microbiol Infect"},{"key":"B79","doi-asserted-by":"publisher","first-page":"10297","DOI":"10.1038\/s41598-024-61025-2","article-title":"Immunoinformatics design of a structural proteins driven multi-epitope candidate vaccine against different sars-cov-2 variants based on fynomer","volume":"14","author":"Sarvmeili","year":"2024","journal-title":"Sci Rep"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.2147\/idr.S264573","article-title":"Design an efficient multi-epitope peptide vaccine candidate against sars-cov-2: An in-silico analysis","volume":"13","author":"Yazdani","year":"2020","journal-title":"Infect Drug Res"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1906485\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T05:35:32Z","timestamp":1788845732000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1906485\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,8]]},"references-count":80,"alternative-id":["10.3389\/fimmu.2026.1906485"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1906485","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,8]]},"article-number":"1906485"}}