{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T04:48:44Z","timestamp":1769834924660,"version":"3.49.0"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T00:00:00Z","timestamp":1719792000000},"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:p>The Zika virus (ZIKV) is an emerging virus associated with the <jats:italic>Flaviviridae<\/jats:italic> family that mainly causes infection in pregnant women and leads to several abnormalities during pregnancy. This virus has unique properties that may lead to pathological diseases. As the virus has the ability to evade immune response, a crucial effort is required to deal with ZIKV. Vaccines are a safe means to control different pathogenic infectious diseases. In the current research, a multi-epitope-based vaccination against ZIKV is being designed using <jats:italic>in silico<\/jats:italic> methods. For the epitope prediction and prioritization phase, ZIKV polyprotein (YP_002790881.1) and flavivirus polyprotein (&amp;gt;YP_009428568.1) were targeted. The predicted B-cell epitopes were used for MHC-I and MHC-II epitope prediction. Afterward, several immunoinformatics filters were applied and nine (REDLWCGSL, MQDLWLLRR, YKKSGITEV, TYTDRRWCF, RDAFPDSNS, KPSLGLINR, ELIGRARVS, AITQGKREE, and EARRSRRAV) epitopes were found to be probably antigenic in nature, non-allergenic, non-toxic, and water soluble without any toxins. Selected epitopes were joined using a particular GPGPG linker to create the base vaccination for epitopes, and an extra EAAAK linker was used to link the adjuvant. A total of 312 amino acids with a molecular weight (MW) of 31.62762 and an instability value of 34.06 were computed in the physicochemical characteristic analysis, indicating that the vaccine design is stable. The molecular docking analysis predicted a binding energy of \u2212329.46 (kcal\/mol) for TLR-3 and \u2212358.54 (kcal\/mol) for TLR-2. Moreover, the molecular dynamics simulation analysis predicted that the vaccine and receptor molecules have stable binding interactions in a dynamic environment. The C-immune simulation analysis predicted that the vaccine has the ability to generate both humoral and cellular immune responses. Based on the design, the vaccine construct has the best efficacy to evoke immune response in theory, but experimental analysis is required to validate the <jats:italic>in silico<\/jats:italic> base approach and ensure its safety.<\/jats:p>","DOI":"10.3389\/fimmu.2024.1426496","type":"journal-article","created":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T04:49:51Z","timestamp":1719809391000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["A novel vaccine construct against Zika virus fever: insights from epitope-based vaccine discovery through molecular modeling and immunoinformatics approaches"],"prefix":"10.3389","volume":"15","author":[{"given":"Metab","family":"Alharbi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdulrahman","family":"Alshammari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jawza F.","family":"Alsabhan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sami I.","family":"Alzarea","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Talal","family":"Alshammari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fawaz","family":"Alasmari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdullah F.","family":"Alasmari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,7,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-018-0055-5","article-title":"The phylogenomics of evolving virus virulence","volume":"19","author":"Geoghegan","year":"2018","journal-title":"Nat Rev Genet"},{"key":"B2","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1016\/j.jiph.2018.04.007","article-title":"Zika virus: epidemiological study and its association with public health risk","volume":"11","author":"Rashed Noor","year":"2019","journal-title":"J Infect Public Health"},{"key":"B3","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1146\/annurev-pathmechdis-031521-034739","article-title":"Pathogenesis of zika virus infection","volume":"18","author":"Giraldo","year":"2023","journal-title":"Annu Rev Pathology: Mech Dis"},{"key":"B4","doi-asserted-by":"publisher","first-page":"898","DOI":"10.3390\/pathogens9110898","article-title":"Zika virus","volume":"9","author":"Masmejan","year":"2020","journal-title":"Pathogens"},{"key":"B5","doi-asserted-by":"publisher","first-page":"294","DOI":"10.3390\/vaccines9030294","article-title":"Zika virus pathogenesis: a battle for immune evasion","volume":"9","author":"Est\u00e9vez-Herrera","year":"2021","journal-title":"Vaccines"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/07391102.2022.2153920","article-title":"Computational study to investigate Proteus mirabilis proteomes for multi-epitope vaccine construct design","author":"Ullah","year":"2022","journal-title":"J Biomolecular Structure Dynamics"},{"key":"B7","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1038\/s41598-021-03990-6","article-title":"In silico construction of a multiepitope Zika virus vaccine using immunoinformatics tools","volume":"12","author":"Antonelli","year":"2022","journal-title":"Sci Rep"},{"key":"B8","doi-asserted-by":"publisher","first-page":"10961","DOI":"10.3390\/ijerph182010961","article-title":"Towards A Novel Multi-Epitopes Chimeric Vaccine for Simulating Strong Immune Responses and Protection against Morganella morganii","volume":"18","author":"Ullah","year":"2021","journal-title":"Int J Environ Res Public Health"},{"key":"B9","doi-asserted-by":"publisher","first-page":"3729","DOI":"10.3390\/ijerph19063729","article-title":"Designing of a Recombinant Multi-Epitopes Based Vaccine against Enterococcus mundtii Using Bioinformatics and Immunoinformatics Approaches","volume":"19","author":"Alharbi","year":"2022","journal-title":"Int J Environ Res Public Health"},{"key":"B10","doi-asserted-by":"publisher","first-page":"189","DOI":"10.3390\/vaccines10020189","article-title":"Designing a Recombinant Vaccine against Providencia rettgeri Using Immunoinformatics Approach","volume":"10","author":"Gul","year":"2022","journal-title":"Vaccines"},{"key":"B11","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":"B12","doi-asserted-by":"publisher","first-page":"8408","DOI":"10.3390\/ijerph19148408","article-title":"Pan-genome analysis of oral bacterial pathogens to predict a potential novel multi-epitopes vaccine candidate","volume":"19","author":"Rida","year":"2022","journal-title":"Int J Environ Res Public Health"},{"key":"B13","doi-asserted-by":"publisher","first-page":"5568","DOI":"10.3390\/ijerph19095568","article-title":"Vaccinomics to design a multi-epitopes vaccine for acinetobacter baumannii","volume":"19","author":"Ud-Din","year":"2022","journal-title":"Int J Environ Res Public Health"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/07391102.2022.2158942","article-title":"Vaccinomics to design a multi-epitope-based vaccine against monkeypox virus using surface-associated proteins","author":"Khan","year":"2022","journal-title":"J Biomolecular Structure Dynamics"},{"key":"B15","doi-asserted-by":"publisher","first-page":"D10","DOI":"10.1093\/nar\/gkaa892","article-title":"Database resources of the national center for biotechnology information","volume":"49","author":"Sayers","year":"2021","journal-title":"Nucleic Acids Res"},{"key":"B16","doi-asserted-by":"publisher","first-page":"378","DOI":"10.3390\/vaccines10030378","article-title":"Design of a multi-epitopes vaccine against hantaviruses: an immunoinformatics and molecular modelling approach","volume":"10","author":"Ismail","year":"2022","journal-title":"Vaccines"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1","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":"B18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1471-2105-14-S6-S4","article-title":"AllerTOP-a server for in silico prediction of allergens","volume":"14","author":"Dimitrov","year":"2013","journal-title":"BMC Bioinf"},{"key":"B19","article-title":"Basic local alignment search tool","author":"Blast","year":"2015","journal-title":"Natl Library Medicine: Natl Center Biotechnol Information"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-020-80899-6","article-title":"In silico analysis of epitope-based vaccine candidate against tuberculosis using reverse vaccinology","volume":"11","author":"Bibi","year":"2021","journal-title":"Sci Rep"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1729","DOI":"10.3390\/vaccines10101729","article-title":"Genome-Based Multi-Antigenic Epitopes Vaccine Construct Designing against Staphylococcus hominis Using Reverse Vaccinology and Biophysical Approaches","volume":"10","author":"Nawaz","year":"2022","journal-title":"Vaccines"},{"key":"B22","doi-asserted-by":"publisher","first-page":"7723","DOI":"10.3390\/ijerph19137723","article-title":"Computer-Aided Multi-Epitope Vaccine Design against Enterobacter xiangfangensis","volume":"19","author":"Alshammari","year":"2022","journal-title":"Int J Environ Res Public Health"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1006","article-title":"The immune epitope database (IEDB): 2018 update","volume":"47","author":"Vita","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"B24","doi-asserted-by":"publisher","first-page":"19","DOI":"10.4137\/DTI.S38458","article-title":"Immunoinformatics approach in designing epitopebased vaccine against meningitis-inducing bacteria (Streptococcus pneumoniae,Neisseria meningitidis,and Haemophilus influenzae type b)","volume":"10","author":"Zahroh","year":"2016","journal-title":"Drug Target Insights"},{"key":"B25","doi-asserted-by":"publisher","first-page":"10742","DOI":"10.3390\/ijerph191710742","article-title":"Novel Chimeric Vaccine Candidate Development against Leptotrichia buccalis","volume":"19","author":"Alshammari","year":"2022","journal-title":"Int J Environ Res Public Health"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/07391102.2022.2125441","article-title":"An integrative reverse vaccinology, immunoinformatic, docking and simulation approaches towards designing of multi-epitopes based vaccine against monkeypox virus","author":"Ullah","year":"2022","journal-title":"J Biomolecular Structure Dynamics"},{"key":"B27","doi-asserted-by":"publisher","first-page":"104705","DOI":"10.1016\/j.compbiomed.2021.104705","article-title":"Pan-vaccinomics approach towards a universal vaccine candidate against WHO priority pathogens to address growing global antibiotic resistance","author":"Ismail","year":"2021","journal-title":"Comput Biol Med"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-022-12269-3","article-title":"In silico analyses and design of chimeric proteins containing epitopes of Bartonella henselae antigens for the control of cat scratch disease","volume":"106","author":"Gon\u00e7alves","year":"2022","journal-title":"Appl Microbiol Biotechnol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"313","DOI":"10.3390\/vaccines8020313","article-title":"Innate immune response against hepatitis C virus: targets for vaccine adjuvants","volume":"8","author":"Sepulveda-Crespo","year":"2020","journal-title":"Vaccines"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1471-2105-14-346","article-title":"Disulfide by Design 2.0: a web-based tool for disulfide engineering in proteins","volume":"14","author":"Craig","year":"2013","journal-title":"BMC Bioinf"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.12-07-02865.1992","article-title":"Spontaneous locomotor hyperactivity in a mouse mutant with a deletion including the Snap gene on chromosome 2","volume":"12","author":"Hess","year":"1992","journal-title":"J Neurosci"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0294663","article-title":"Computational design of experimentally validated multi-epitopes vaccine against hepatitis E virus: An immunological approach","volume":"18","author":"Anwar","year":"2023","journal-title":"PloS One"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1042997","article-title":"Immunoinformatic-based design of immune-boosting multiepitope subunit vaccines against monkeypox virus and validation through molecular dynamics and immune simulation","volume":"13","author":"Suleman","year":"2022","journal-title":"Front Immunol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.21203\/rs.3.rs-3027574\/v1","article-title":"Sequencing-based protein\u2013protein interaction analysis provides an immune gene network for understanding white body immune response mechanisms against Poly I: C stimulation in Amphioctopus fangsiao","volume":"6","author":"Chen","year":"2023","journal-title":"Comp Immunol Rep."},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2020.105258","article-title":"Vaccinomics to design a novel single chimeric subunit vaccine for broad-spectrum immunological applications targeting nosocomial Enterobacteriaceae pathogens","volume":"146","author":"Ismail","year":"2020","journal-title":"Eur J Pharm Sci"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2016.169","article-title":"The ClusPro web server for protein\u2013protein docking","volume":"12","author":"Kozakov","year":"2017","journal-title":"Nat Protoc"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1886","DOI":"10.3390\/vaccines10111886","article-title":"Computational Design of a Chimeric Vaccine against Plesiomonas shigelloides Using Pan-Genome and Reverse Vaccinology","volume":"10","author":"Mushtaq","year":"2022","journal-title":"Vaccines"},{"key":"B38","first-page":"29","article-title":"The FF14SB force field","volume":"14","author":"Case","year":"2014","journal-title":"Amber"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.4208\/cicp.210711.121011s","article-title":"Examining electrostatic influences on base-flipping: a comparison of TIP3P and GB solvent models","volume":"13","author":"Brice","year":"2013","journal-title":"Commun Comput Phys"},{"key":"B40","doi-asserted-by":"publisher","first-page":"150","DOI":"10.3390\/tropicalmed5040150","article-title":"Dengue and Zika viruses: Epidemiological history, potential therapies, and promising vaccines","volume":"5","author":"Silva","year":"2020","journal-title":"Trop Med Infect Dis"},{"key":"B41","doi-asserted-by":"publisher","first-page":"174","DOI":"10.5455\/javar.","article-title":"Epitope-based vaccine as a universal vaccination strategy against Toxoplasma gondii infection: a mini-review","volume":"6","author":"Hajissa","year":"2019","journal-title":"J Advanced Veterinary Anim Res"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2022.2125441","article-title":"An integrative reverse vaccinology, immunoinformatic, docking and simulation approaches towards designing of multi-epitopes based vaccine against monkeypox virus","volume":"41","author":"Ullah","year":"2023","journal-title":"J Biomolecular Structure Dynamics"},{"key":"B43","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s13721-021-00339-x","article-title":"T-cell epitope-based vaccine designing against Orthohantavirus: a causative agent of deadly cardio-pulmonary disease","volume":"11","author":"Joshi","year":"2022","journal-title":"Network Modeling Anal Health Inf Bioinf"},{"key":"B44","doi-asserted-by":"publisher","first-page":"263","DOI":"10.3390\/vaccines11020263","article-title":"Proteome-wide Screening of Potential Vaccine Targets against Brucella melitensis","volume":"11","author":"Malik","year":"2023","journal-title":"Vaccines"},{"key":"B45","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s12033-023-00949-y","article-title":"An in silico multi-epitopes vaccine ensemble and characterization against nosocomial proteus penneri","author":"Ullah","year":"2023","journal-title":"Mol Biotechnol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2023.2219324","article-title":"Design and validation of a novel multi-epitopes vaccine against hantavirus","volume":"42","author":"Almanaa","year":"2024","journal-title":"J Biomolecular Structure Dynamics"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2023.2212793","article-title":"A computational quest for identifying potential vaccine candidates against Moraxella lacunata: a multi-pronged approach","volume":"42","author":"Ullah","year":"2024","journal-title":"J Biomolecular Structure Dynamics"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1035924","article-title":"Immuno-informatics profiling of monkeypox virus cell surface binding protein for designing a next generation multi-valent peptide-based vaccine","volume":"13","author":"Yousaf","year":"2022","journal-title":"Front Immunol"},{"key":"B49","doi-asserted-by":"publisher","first-page":"1192","DOI":"10.3390\/vaccines10081192","article-title":"Design of multi-epitope vaccine for staphylococcus saprophyticus: pan-genome and reverse vaccinology approach","volume":"10","author":"Yousaf","year":"2022","journal-title":"Vaccines"},{"key":"B50","doi-asserted-by":"publisher","first-page":"1580","DOI":"10.3390\/vaccines10101580","article-title":"Computational Based Designing of a Multi-Epitopes Vaccine against Burkholderia mallei","volume":"10","author":"Irfan","year":"2022","journal-title":"Vaccines"},{"key":"B51","doi-asserted-by":"publisher","first-page":"105592","DOI":"10.1016\/j.micpath.2022.105592","article-title":"Characterization of proteome wide antigenic epitopes to design proteins specific and proteome-wide ensemble vaccines against heartland virus using structural vaccinology and immune simulation approaches","volume":"168","author":"Suleman","year":"2022","journal-title":"Microbial Pathogenesis"},{"key":"B52","doi-asserted-by":"publisher","first-page":"665","DOI":"10.3390\/vaccines10050665","article-title":"Designing of a Novel Multi-Antigenic Epitope-Based Vaccine against E. hormaechei: An Intergraded Reverse Vaccinology and Immunoinformatics Approach","volume":"10","author":"Albekairi","year":"2022","journal-title":"Vaccines"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1426496\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,10]],"date-time":"2024-07-10T13:58:18Z","timestamp":1720619898000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1426496\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,1]]},"references-count":52,"alternative-id":["10.3389\/fimmu.2024.1426496"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2024.1426496","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,1]]},"article-number":"1426496"}}