{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:29:08Z","timestamp":1789000148962,"version":"build-2803163510"},"reference-count":125,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2024,9,26]],"date-time":"2024-09-26T00:00:00Z","timestamp":1727308800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014166","name":"Philippine Council for Agriculture, Aquatic and Natural Resources Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100014166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>\n                    The resurgence of the Nipah virus (NiV) in 2023 has raised concerns for another potentially severe pandemic, given its history of high mortality from previous outbreaks. Unfortunately, no therapeutics and vaccines have been available for the virus. This study used immunoinformatics and molecular modeling to design and evaluate a multi-epitope subunit vaccine targeting NiV. The designed vaccine construct aims to stimulate immune responses in humans and two other intermediate animal hosts of the virus\u2014swine and equine. Using several epitope prediction tools, ten peptides that induced B-lymphocyte responses, 17 peptides that induced cytotoxic T-lymphocyte (CTL) responses, and 12 peptides that induced helper T-lymphocyte (HTL) responses were mapped from nine NiV protein sequences. However, the CTL and HTL-inducing peptides were reduced to ten and eight, respectively, following molecular docking and dynamics. These screened peptides exhibited stability with 30 common major histocompatibility complex (MHC) receptors found in humans, swine, and equine. All peptides were linked using peptide linkers to form the multi-epitope construct and various adjuvants were tested to enhance its immunogenicity. The vaccine construct with resuscitation-promoting factor E (RpfE) adjuvant was selected as the final design based on its favorable physicochemical properties and superior immune response profile. Molecular docking was used to visualize the interaction of the vaccine to toll-like receptor 4 (TLR4), while molecular dynamics confirmed the structural stability of this interaction. Physicochemical property evaluation and computational simulations showed that the designed vaccine construct exhibited favorable properties and elicited higher antibody titers than the six multi-epitope NiV vaccine designs available in the literature. Further\n                    <jats:italic>in vivo<\/jats:italic>\n                    and\n                    <jats:italic>in vitro<\/jats:italic>\n                    experiments are necessary to validate the immunogenicity conferred by the designed vaccine construct and its epitope components. This study demonstrates the capability of computational methodologies in rational vaccine design and highlights the potential of cross-species vaccination strategies for mitigating potential NiV threats.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0310703","type":"journal-article","created":{"date-parts":[[2024,9,26]],"date-time":"2024-09-26T13:29:52Z","timestamp":1727357392000},"page":"e0310703","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":14,"title":["Advancing one health vaccination: In silico design and evaluation of a multi-epitope subunit vaccine against Nipah virus for cross-species immunization using immunoinformatics and molecular modeling"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-9839-9315","authenticated-orcid":true,"given":"Edward Coralde","family":"Banico","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ella Mae Joy Sinco","family":"Sira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren Emily","family":"Fajardo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4708-4625","authenticated-orcid":true,"given":"Albert Neil Gura","family":"Dulay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1979-5571","authenticated-orcid":true,"given":"Nyzar Mabeth Obenio","family":"Odchimar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alea Maurice","family":"Simbulan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8861-7923","authenticated-orcid":true,"given":"Fredmoore Legaspi","family":"Orosco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,9,26]]},"reference":[{"key":"pone.0310703.ref001","doi-asserted-by":"crossref","DOI":"10.1177\/20499361231208535","article-title":"Recent Nipah virus outbreak in India: lessons and imperatives","volume":"10","author":"S Srivastava","year":"2023","journal-title":"Therapeutic Advances in Infectious Disease"},{"issue":"12","key":"pone.0310703.ref002","doi-asserted-by":"crossref","first-page":"1855","DOI":"10.1093\/infdis\/jiy611","article-title":"Nipah Virus Outbreaks: Still Small but Extremely Lethal","volume":"219","author":"CF Spiropoulou","year":"2019","journal-title":"The Journal of Infectious Diseases"},{"issue":"1","key":"pone.0310703.ref003","doi-asserted-by":"crossref","first-page":"24","DOI":"10.3390\/tropicalmed6010024","article-title":"Evolution of Nipah Virus Infection: Past, Present, and Future Considerations","volume":"6","author":"N Hauser","year":"2021","journal-title":"Trop Med Infect Dis"},{"issue":"5470","key":"pone.0310703.ref004","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1126\/science.288.5470.1432","article-title":"Nipah Virus: A Recently Emergent Deadly Paramyxovirus","volume":"288","author":"KB Chua","year":"2000","journal-title":"Science"},{"issue":"1","key":"pone.0310703.ref005","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1080\/01652176.2019.1580827","article-title":"Nipah virus: epidemiology, pathology, immunobiology and advances in diagnosis, vaccine designing and control strategies\u2014a comprehensive review","volume":"39","author":"RK Singh","year":"2019","journal-title":"Vet Q"},{"issue":"5","key":"pone.0310703.ref006","doi-asserted-by":"crossref","first-page":"946","DOI":"10.4269\/ajtmh.2011.10-0567","article-title":"Pteropid bats are confirmed as the reservoir hosts of henipaviruses: a comprehensive experimental study of virus transmission","volume":"85","author":"K Halpin","year":"2011","journal-title":"Am J Trop Med Hyg"},{"key":"pone.0310703.ref007","doi-asserted-by":"crossref","first-page":"16","DOI":"10.3389\/fvets.2019.00016","article-title":"Vaccine Development for Nipah Virus Infection in Pigs","volume":"6","author":"RK McLean","year":"2019","journal-title":"Front Vet Sci"},{"issue":"2","key":"pone.0310703.ref008","doi-asserted-by":"crossref","first-page":"328","DOI":"10.3201\/eid2102.141433","article-title":"Outbreak of Henipavirus Infection, Philippines, 2014","volume":"21","author":"PKG Ching","year":"2015","journal-title":"Emerg Infect Dis"},{"key":"pone.0310703.ref009","first-page":"1","article-title":"From antibiotic to antiviral: computational screening reveals a multi-targeting antibiotic from Streptomyces spp. against Nipah virus fusion proteins","author":"NMO Odchimar","year":"2024","journal-title":"Molecular Diversity"},{"issue":"9","key":"pone.0310703.ref010","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.5455\/OVJ.2023.v13.i9.1","article-title":"Advancing the frontiers: Revolutionary control and prevention paradigms against Nipah virus","volume":"13","author":"FL Orosco","year":"2023","journal-title":"Open Vet J"},{"key":"pone.0310703.ref011","article-title":"Understanding the Global Transmission and Demographic Distribution of Nipah Virus (NiV)","volume":"16","author":"M Rezwan","year":"2023","journal-title":"Research Journal of Pharmacy and Technology"},{"key":"pone.0310703.ref012","doi-asserted-by":"crossref","first-page":"106","DOI":"10.5455\/jabet.2024.d10","article-title":"Recent advances in peptide-based nanovaccines for re-emerging and emerging infectious diseases","volume":"7","author":"F Orosco","year":"2024","journal-title":"Journal of Advanced Biotechnology and Experimental Therapeutics"},{"key":"pone.0310703.ref013","doi-asserted-by":"crossref","first-page":"18","DOI":"10.22159\/ijap.2024v16i1.49563","article-title":"Navigating the landscape of adjuvants for subunit vaccines: Recent advances and future perspective","author":"F Orosco","year":"2024","journal-title":"International Journal of Applied Pharmaceutics"},{"key":"pone.0310703.ref014","first-page":"2025011","article-title":"Current strategies, advances, and challenges in multi-epitope subunit vaccine development for African swine fever virus","volume":"23","author":"EMJ Sira","year":"2024","journal-title":"Veterinary Integrative Sciences"},{"key":"pone.0310703.ref015","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/978-0-387-79208-8_3","article-title":"Epitope-Based Immunome-Derived Vaccines: A Strategy for Improved Design and Safety","volume-title":"Clinical Applications of Immunomics. Immunomics Reviews","author":"AS De Groot","year":"2009"},{"issue":"5","key":"pone.0310703.ref016","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.5455\/OVJ.2024.v14.i5.18","article-title":"Immunoinformatics approach for designing a multi-epitope subunit vaccine against porcine epidemic diarrhea virus genotype IIA spike protein","volume":"14","author":"EMJS Sira","year":"2024","journal-title":"Open Veterinary Journal"},{"issue":"14","key":"pone.0310703.ref017","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.2174\/092986706777441922","article-title":"Design of Peptide-Based Vaccines for Cancer","volume":"13","author":"G Pietersz","year":"2006","journal-title":"CMC"},{"issue":"4","key":"pone.0310703.ref018","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1080\/07391102.2020.1734088","article-title":"Designing of a multi-epitope vaccine candidate against Nipah virus by in silico approach: a putative prophylactic solution for the deadly virus","volume":"39","author":"P Majee","year":"2021","journal-title":"Journal of Biomolecular Structure and Dynamics"},{"issue":"3","key":"pone.0310703.ref019","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.1007\/s10989-021-10219-7","article-title":"Anticipation of Antigenic Sites for the Goal of Vaccine Designing Against Nipah Virus: An Immunoinformatics Inquisitive Quest","volume":"27","author":"Sk Sharma","year":"2021","journal-title":"Int J Pept Res Ther"},{"issue":"4","key":"pone.0310703.ref020","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1007\/s10989-022-10431-z","article-title":"An Immunoinformatics Prediction of Novel Multi-Epitope Vaccines Candidate Against Surface Antigens of Nipah Virus","volume":"28","author":"MM Rahman","year":"2022","journal-title":"Int J Pept Res Ther"},{"issue":"3","key":"pone.0310703.ref021","doi-asserted-by":"crossref","first-page":"e0282580","DOI":"10.1371\/journal.pone.0282580","article-title":"Exploring the structural basis to develop efficient multi-epitope vaccines displaying interaction with HLA and TAP and TLR3 molecules to prevent NIPAH infection, a global threat to human health","volume":"18","author":"S Srivastava","year":"2023","journal-title":"PLoS ONE"},{"issue":"1","key":"pone.0310703.ref022","doi-asserted-by":"crossref","first-page":"212","DOI":"10.22207\/JPAM.15.1.16","article-title":"In-silico Design of Multi-epitope Vaccine against Nipah Virus using Immunoinformatics Approach","volume":"15","author":"S Raju","year":"2021","journal-title":"J Pure Appl Microbiol"},{"issue":"12","key":"pone.0310703.ref023","doi-asserted-by":"crossref","first-page":"101826","DOI":"10.1016\/j.jsps.2023.101826","article-title":"An integrated multi-pronged reverse vaccinology and biophysical approaches for identification of potential vaccine candidates against Nipah virus","volume":"31","author":"A Albutti","year":"2023","journal-title":"Saudi Pharmaceutical Journal"},{"issue":"8","key":"pone.0310703.ref024","doi-asserted-by":"crossref","first-page":"13069","DOI":"10.1021\/acsomega.9b00944","article-title":"Strategic Development of a Next-Generation Multi-Epitope Vaccine To Prevent Nipah Virus Zoonotic Infection","volume":"4","author":"R Ojha","year":"2019","journal-title":"ACS Omega"},{"issue":"46","key":"pone.0310703.ref025","doi-asserted-by":"crossref","first-page":"5321","DOI":"10.1016\/j.vaccine.2013.09.029","article-title":"Vaccines against diseases transmitted from animals to humans: A one health paradigm","volume":"31","author":"TP Monath","year":"2013","journal-title":"Vaccine"},{"issue":"12","key":"pone.0310703.ref026","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1038\/s41577-021-00567-2","article-title":"Using cross-species vaccination approaches to counter emerging infectious diseases","volume":"21","author":"GM Warimwe","year":"2021","journal-title":"Nat Rev Immunol"},{"issue":"1","key":"pone.0310703.ref027","doi-asserted-by":"crossref","first-page":"20617","DOI":"10.1038\/srep20617","article-title":"Chimpanzee Adenovirus Vaccine Provides Multispecies Protection against Rift Valley Fever","volume":"6","author":"GM Warimwe","year":"2016","journal-title":"Sci Rep"},{"issue":"7","key":"pone.0310703.ref028","doi-asserted-by":"crossref","first-page":"e40385","DOI":"10.1371\/journal.pone.0040385","article-title":"A Novel Chimpanzee Adenovirus Vector with Low Human Seroprevalence: Improved Systems for Vector Derivation and Comparative Immunogenicity","volume":"7","author":"MDJ Dicks","year":"2012","journal-title":"PLOS ONE"},{"issue":"D1","key":"pone.0310703.ref029","doi-asserted-by":"crossref","first-page":"D20","DOI":"10.1093\/nar\/gkab1112","article-title":"Database resources of the national center for biotechnology information","volume":"50","author":"EW Sayers","year":"2022","journal-title":"Nucleic Acids Research"},{"issue":"W1","key":"pone.0310703.ref030","doi-asserted-by":"crossref","first-page":"W29","DOI":"10.1093\/nar\/gkt282","article-title":"BLAST: a more efficient report with usability improvements","volume":"41","author":"GM Boratyn","year":"2013","journal-title":"Nucleic Acids Research"},{"issue":"1","key":"pone.0310703.ref031","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1002\/pro.3290","article-title":"Clustal Omega for making accurate alignments of many protein sequences","volume":"27","author":"F Sievers","year":"2018","journal-title":"Protein Sci"},{"issue":"suppl2","key":"pone.0310703.ref032","doi-asserted-by":"crossref","first-page":"W35","DOI":"10.1093\/nar\/gkn211","article-title":"PVS: a web server for protein sequence variability analysis tuned to facilitate conserved epitope discovery","volume":"36","author":"M Garcia-Boronat","year":"2008","journal-title":"Nucleic Acids Research"},{"issue":"12","key":"pone.0310703.ref033","doi-asserted-by":"crossref","first-page":"e4497","DOI":"10.1002\/pro.4497","article-title":"BepiPred-3.0: Improved B-cell epitope prediction using protein language models","volume":"31","author":"JN Clifford","year":"2022","journal-title":"Protein Science"},{"issue":"9","key":"pone.0310703.ref034","doi-asserted-by":"crossref","first-page":"e45152","DOI":"10.1371\/journal.pone.0045152","article-title":"SVMTriP: a method to predict antigenic epitopes using support vector machine to integrate tri-peptide similarity and propensity","volume":"7","author":"B Yao","year":"2012","journal-title":"PLoS One"},{"issue":"1","key":"pone.0310703.ref035","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1002\/prot.21078","article-title":"Prediction of continuous B-cell epitopes in an antigen using recurrent neural network","volume":"65","author":"S Saha","year":"2006","journal-title":"Proteins: Structure, Function, and Bioinformatics"},{"key":"pone.0310703.ref036","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1007\/978-1-4939-2999-3_28","volume-title":"Peptide Antibodies: Methods and Protocols. Methods in Molecular Biology","author":"H Singh","year":"2015"},{"issue":"22","key":"pone.0310703.ref037","doi-asserted-by":"crossref","first-page":"E2046","DOI":"10.1073\/pnas.1305227110","article-title":"Comprehensive analysis of dengue virus-specific responses supports an HLA-linked protective role for CD8+ T cells","volume":"110","author":"D Weiskopf","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pone.0310703.ref038","doi-asserted-by":"crossref","first-page":"100019","DOI":"10.1016\/j.immuno.2022.100019","article-title":"In silico design and evaluation of a multi-epitope and multi-antigenic African swine fever vaccine","volume":"8","author":"AKG Buan","year":"2022","journal-title":"ImmunoInformatics"},{"issue":"12","key":"pone.0310703.ref039","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.3390\/pathogens9121078","article-title":"Computational Analysis of African Swine Fever Virus Protein Space for the Design of an Epitope-Based Vaccine Ensemble","volume":"9","author":"A Ros-Lucas","year":"2020","journal-title":"Pathogens"},{"key":"pone.0310703.ref040","doi-asserted-by":"crossref","first-page":"319","DOI":"10.4103\/bbrj.bbrj_79_22","article-title":"Immunoinformatics-based identification of highly conserved cytotoxic T-cell epitopes in polyprotein pp220 of african swine fever virus","volume":"6","author":"AKA Juan","year":"2022","journal-title":"Biomedical and Biotechnology Research Journal"},{"issue":"1","key":"pone.0310703.ref041","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1038\/s41598-023-51005-3","article-title":"Immunoinformatics-guided approach for designing a pan-proteome multi-epitope subunit vaccine against African swine fever virus","volume":"14","author":"AM Simbulan","year":"2024","journal-title":"Sci Rep"},{"issue":"3","key":"pone.0310703.ref042","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1007\/s00251-011-0579-8","article-title":"NetMHCcons: a consensus method for the major histocompatibility complex class I predictions","volume":"64","author":"E Karosiene","year":"2012","journal-title":"Immunogenetics"},{"issue":"6","key":"pone.0310703.ref043","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1007\/s00251-010-0441-4","article-title":"NetCTLpan: pan-specific MHC class I pathway epitope predictions","volume":"62","author":"T Stranzl","year":"2010","journal-title":"Immunogenetics"},{"issue":"10","key":"pone.0310703.ref044","doi-asserted-by":"crossref","first-page":"e1003266","DOI":"10.1371\/journal.pcbi.1003266","article-title":"Properties of MHC Class I Presented Peptides That Enhance Immunogenicity","volume":"9","author":"JJA Calis","year":"2013","journal-title":"PLoS Comput Biol"},{"issue":"6","key":"pone.0310703.ref045","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1007\/s00251-011-0513-0","article-title":"Functional classification of class II human leukocyte antigen (HLA) molecules reveals seven different supertypes and a surprising degree of repertoire sharing across supertypes","volume":"63","author":"J Greenbaum","year":"2011","journal-title":"Immunogenetics"},{"key":"pone.0310703.ref046","doi-asserted-by":"crossref","first-page":"637682","DOI":"10.3389\/fvets.2021.637682","article-title":"Diversity of the Swine Leukocyte Antigen Class I and II in Commercial Pig Populations","volume":"8","author":"N Techakriengkrai","year":"2021","journal-title":"Front Vet Sci"},{"issue":"W1","key":"pone.0310703.ref047","doi-asserted-by":"crossref","first-page":"W449","DOI":"10.1093\/nar\/gkaa379","article-title":"NetMHCpan-4.1 and NetMHCIIpan-4.0: improved predictions of MHC antigen presentation by concurrent motif deconvolution and integration of MS MHC eluted ligand data","volume":"48","author":"B Reynisson","year":"2020","journal-title":"Nucleic Acids Res"},{"issue":"47","key":"pone.0310703.ref048","doi-asserted-by":"crossref","first-page":"eadj6367","DOI":"10.1126\/sciadv.adj6367","article-title":"Accurate prediction of HLA class II antigen presentation across all loci using tailored data acquisition and refined machine learning","volume":"9","author":"JB Nilsson","year":"2023","journal-title":"Science Advances"},{"key":"pone.0310703.ref049","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2018.01369","article-title":"Predicting HLA CD4 Immunogenicity in Human Populations","volume":"9","author":"SK Dhanda","year":"2018","journal-title":"Frontiers in Immunology"},{"key":"pone.0310703.ref050","doi-asserted-by":"crossref","first-page":"106929","DOI":"10.1016\/j.compbiomed.2023.106929","article-title":"TNFepitope: A webserver for the prediction of TNF\u03b1 inducing epitopes","volume":"160","author":"A Dhall","year":"2023","journal-title":"Computers in Biology and Medicine"},{"issue":"2","key":"pone.0310703.ref051","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1093\/bib\/bbaa259","article-title":"Computer-aided prediction and design of IL-6 inducing peptides: IL-6 plays a crucial role in COVID-19","volume":"22","author":"A Dhall","year":"2021","journal-title":"Briefings in Bioinformatics"},{"issue":"1","key":"pone.0310703.ref052","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/1745-6150-8-30","article-title":"Designing of interferon-gamma inducing MHC class-II binders","volume":"8","author":"SK Dhanda","year":"2013","journal-title":"Biology Direct"},{"issue":"1","key":"pone.0310703.ref053","doi-asserted-by":"crossref","first-page":"4","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":"IA Doytchinova","year":"2007","journal-title":"BMC Bioinformatics"},{"issue":"6","key":"pone.0310703.ref054","doi-asserted-by":"crossref","first-page":"2278","DOI":"10.1007\/s00894-014-2278-5","article-title":"AllerTOP v.2\u2013a server for in silico prediction of allergens","volume":"20","author":"I Dimitrov","year":"2014","journal-title":"J Mol Model"},{"issue":"9","key":"pone.0310703.ref055","doi-asserted-by":"crossref","first-page":"e73957","DOI":"10.1371\/journal.pone.0073957","article-title":"In Silico Approach for Predicting Toxicity of Peptides and Proteins","volume":"8","author":"Consortium OSDD","year":"2013","journal-title":"PLOS ONE"},{"issue":"3-4","key":"pone.0310703.ref056","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1006\/biol.2001.0297","article-title":"The Development of Multi-epitope Vaccines: Epitope Identification, Vaccine Design and Clinical Evaluation","volume":"29","author":"A Sette","year":"2001","journal-title":"Biologicals"},{"issue":"3","key":"pone.0310703.ref057","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1007\/s00251-009-0420-9","article-title":"Analysis of MHC class I genes across horse MHC haplotypes","volume":"62","author":"RL Tallmadge","year":"2010","journal-title":"Immunogenetics"},{"issue":"D1","key":"pone.0310703.ref058","doi-asserted-by":"crossref","first-page":"D1234","DOI":"10.1093\/nar\/gks1140","article-title":"IPD\u2014the Immuno Polymorphism Database","volume":"41","author":"J Robinson","year":"2013","journal-title":"Nucleic Acids Research"},{"issue":"W1","key":"pone.0310703.ref059","doi-asserted-by":"crossref","first-page":"W296","DOI":"10.1093\/nar\/gky427","article-title":"SWISS-MODEL: homology modelling of protein structures and complexes","volume":"46","author":"A Waterhouse","year":"2018","journal-title":"Nucleic Acids Research"},{"issue":"13","key":"pone.0310703.ref060","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera\u2013a visualization system for exploratory research and analysis","volume":"25","author":"EF Pettersen","year":"2004","journal-title":"J Comput Chem"},{"issue":"Web Server issue","key":"pone.0310703.ref061","doi-asserted-by":"crossref","first-page":"W384","DOI":"10.1093\/nar\/gkt458","article-title":"GalaxyRefine: Protein structure refinement driven by side-chain repacking","volume":"41","author":"L Heo","year":"2013","journal-title":"Nucleic Acids Res"},{"issue":"9","key":"pone.0310703.ref062","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1002\/pro.5560020916","article-title":"Verification of protein structures: patterns of nonbonded atomic interactions","volume":"2","author":"C Colovos","year":"1993","journal-title":"Protein Sci"},{"issue":"2","key":"pone.0310703.ref063","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1107\/S0021889892009944","article-title":"PROCHECK: a program to check the stereochemical quality of protein structures","volume":"26","author":"RA Laskowski","year":"1993","journal-title":"Journal of Applied Crystallography"},{"issue":"1","key":"pone.0310703.ref064","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/nar\/28.1.235","article-title":"The Protein Data Bank","volume":"28","author":"HM Berman","year":"2000","journal-title":"Nucleic Acids Research"},{"issue":"W1","key":"pone.0310703.ref065","doi-asserted-by":"crossref","first-page":"W443","DOI":"10.1093\/nar\/gky357","article-title":"HPEPDOCK: a web server for blind peptide-protein docking based on a hierarchical algorithm","volume":"46","author":"P Zhou","year":"2018","journal-title":"Nucleic Acids Res"},{"issue":"3","key":"pone.0310703.ref066","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1007\/s00357-014-9161-z","article-title":"Ward\u2019s Hierarchical Agglomerative Clustering Method: Which Algorithms Implement Ward\u2019s Criterion?","volume":"31","author":"F Murtagh","year":"2014","journal-title":"J Classif"},{"key":"pone.0310703.ref067","unstructured":"Posit team. RStudio: Integrated Development Environment for R; 2023. Available from: http:\/\/www.posit.co\/."},{"issue":"1","key":"pone.0310703.ref068","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1021\/ci100275a","article-title":"Assessing the Performance of the MM\/PBSA and MM\/GBSA Methods. 1. The Accuracy of Binding Free Energy Calculations Based on Molecular Dynamics Simulations","volume":"51","author":"T Hou","year":"2011","journal-title":"J Chem Inf Model"},{"issue":"25","key":"pone.0310703.ref069","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1002\/jcc.23354","article-title":"CHARMM36 all-atom additive protein force field: Validation based on comparison to NMR data","volume":"34","author":"J Huang","year":"2013","journal-title":"J Comput Chem"},{"key":"pone.0310703.ref070","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.softx.2015.06.001","article-title":"GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers","volume":"1","author":"MJ Abraham","year":"2015","journal-title":"SoftwareX"},{"issue":"10","key":"pone.0310703.ref071","doi-asserted-by":"crossref","first-page":"6281","DOI":"10.1021\/acs.jctc.1c00645","article-title":"gmx_MMPBSA: A New Tool to Perform End-State Free Energy Calculations with GROMACS","volume":"17","author":"MS Vald\u00e9s-Tresanco","year":"2021","journal-title":"J Chem Theory Comput"},{"issue":"4","key":"pone.0310703.ref072","doi-asserted-by":"crossref","first-page":"e9862","DOI":"10.1371\/journal.pone.0009862","article-title":"Computational Immunology Meets Bioinformatics: The Use of Prediction Tools for Molecular Binding in the Simulation of the Immune System","volume":"5","author":"N Rapin","year":"2010","journal-title":"PLOS ONE"},{"issue":"17","key":"pone.0310703.ref073","doi-asserted-by":"crossref","first-page":"2200","DOI":"10.1093\/bioinformatics\/btp386","article-title":"SOLpro: accurate sequence-based prediction of protein solubility","volume":"25","author":"CN Magnan","year":"2009","journal-title":"Bioinformatics"},{"key":"pone.0310703.ref074","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1385\/1-59259-890-0:571","volume-title":"The Proteomics Protocols Handbook. Springer Protocols Handbooks","author":"E Gasteiger","year":"2005"},{"issue":"6","key":"pone.0310703.ref075","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1038\/s41592-022-01488-1","article-title":"ColabFold: making protein folding accessible to all","volume":"19","author":"M Mirdita","year":"2022","journal-title":"Nat Methods"},{"issue":"7873","key":"pone.0310703.ref076","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein structure prediction with AlphaFold","volume":"596","author":"J Jumper","year":"2021","journal-title":"Nature"},{"issue":"12","key":"pone.0310703.ref077","doi-asserted-by":"crossref","first-page":"1684","DOI":"10.1002\/prot.26585","article-title":"Integrating deep learning, threading alignments, and a multi-MSA strategy for high-quality protein monomer and complex structure prediction in CASP15","volume":"91","author":"W Zheng","year":"2023","journal-title":"Proteins"},{"issue":"6557","key":"pone.0310703.ref078","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1126\/science.abj8754","article-title":"Accurate prediction of protein structures and interactions using a three-track neural network","volume":"373","author":"M Baek","year":"2021","journal-title":"Science"},{"issue":"suppl2","key":"pone.0310703.ref079","doi-asserted-by":"crossref","first-page":"W407","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":"M Wiederstein","year":"2007","journal-title":"Nucleic Acids Research"},{"key":"pone.0310703.ref080","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1186\/1471-2105-9-514","article-title":"ElliPro: a new structure-based tool for the prediction of antibody epitopes","volume":"9","author":"J Ponomarenko","year":"2008","journal-title":"BMC bioinformatics"},{"key":"pone.0310703.ref081","unstructured":"Schr\u00f6dinger, LLC. The PyMOL Molecular Graphics System, Version 1.8; 2015."},{"key":"pone.0310703.ref082","doi-asserted-by":"crossref","first-page":"5.6.1","DOI":"10.1002\/cpbi.3","article-title":"Comparative Protein Structure Modeling Using MODELLER","volume":"54","author":"B Webb","year":"2016","journal-title":"Curr Protoc Bioinformatics"},{"issue":"2","key":"pone.0310703.ref083","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/nprot.2016.169","article-title":"The ClusPro web server for protein\u2013protein docking","volume":"12","author":"D Kozakov","year":"2017","journal-title":"Nat Protoc"},{"issue":"3","key":"pone.0310703.ref084","doi-asserted-by":"crossref","first-page":"107985","DOI":"10.1016\/j.jsb.2023.107985","article-title":"The SIRAH force field: A suite for simulations of complex biological systems at the coarse-grained and multiscale levels","volume":"215","author":"F Klein","year":"2023","journal-title":"Journal of Structural Biology"},{"key":"pone.0310703.ref085","doi-asserted-by":"crossref","first-page":"108133","DOI":"10.1016\/j.compbiolchem.2024.108133","article-title":"High-throughput virtual screening of Streptomyces spp. metabolites as antiviral inhibitors against the Nipah virus matrix protein","volume":"112","author":"MAB Macalalad","year":"2024","journal-title":"Computational Biology and Chemistry"},{"issue":"14","key":"pone.0310703.ref086","doi-asserted-by":"crossref","first-page":"10039","DOI":"10.1039\/D4RA00819G","article-title":"In silico identification of multi-target inhibitors from medicinal fungal metabolites against the base excision repair pathway proteins of African swine fever virus","volume":"14","author":"MAB Macalalad","year":"2024","journal-title":"RSC Advances"},{"issue":"1","key":"pone.0310703.ref087","doi-asserted-by":"crossref","first-page":"346","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":"DB Craig","year":"2013","journal-title":"BMC Bioinformatics"},{"key":"pone.0310703.ref088","doi-asserted-by":"crossref","first-page":"248429","DOI":"10.3389\/fimmu.2017.00292","article-title":"Major Histocompatibility Complex (MHC) Class I and MHC Class II Proteins: Conformational Plasticity in Antigen Presentation","volume":"8","author":"M Wieczorek","year":"2017","journal-title":"Front Immunol"},{"issue":"1","key":"pone.0310703.ref089","doi-asserted-by":"crossref","first-page":"3238","DOI":"10.1038\/s41598-021-81749-9","article-title":"An in silico deep learning approach to multi-epitope vaccine design: a SARS-CoV-2 case study","volume":"11","author":"Z Yang","year":"2021","journal-title":"Sci Rep"},{"issue":"6","key":"pone.0310703.ref090","doi-asserted-by":"crossref","first-page":"3210","DOI":"10.3390\/ijms22063210","article-title":"Linear B-Cell Epitope Prediction for In Silico Vaccine Design: A Performance Review of Methods Available via Command-Line Interface","volume":"22","author":"KA Galanis","year":"2021","journal-title":"International Journal of Molecular Sciences"},{"issue":"1","key":"pone.0310703.ref091","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/s00251-005-0781-7","article-title":"The role of the proteasome in generating cytotoxic T-cell epitopes: insights obtained from improved predictions of proteasomal cleavage","volume":"57","author":"M Nielsen","year":"2005","journal-title":"Immunogenetics"},{"issue":"4","key":"pone.0310703.ref092","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.4049\/jimmunol.171.4.1741","article-title":"Identifying MHC Class I Epitopes by Predicting the TAP Transport Efficiency of Epitope Precursors","volume":"171","author":"B Peters","year":"2003","journal-title":"The Journal of Immunology"},{"issue":"8","key":"pone.0310703.ref093","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/S0161-5890(98)00059-5","article-title":"Substrate selection by transporters associated with antigen processing occurs during peptide binding to TAP","volume":"35","author":"B Gubler","year":"1998","journal-title":"Molecular Immunology"},{"key":"pone.0310703.ref094","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.meegid.2016.08.037","article-title":"Computational prediction and analysis of potential antigenic CTL epitopes in Zika virus: A first step towards vaccine development","volume":"45","author":"MR Dikhit","year":"2016","journal-title":"Infection, Genetics and Evolution: Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases"},{"issue":"2","key":"pone.0310703.ref095","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1038\/cmi.2017.92","article-title":"Multi-epitope vaccines: a promising strategy against tumors and viral infections","volume":"15","author":"L Zhang","year":"2018","journal-title":"Cell Mol Immunol"},{"key":"pone.0310703.ref096","doi-asserted-by":"crossref","first-page":"960859","DOI":"10.1155\/2015\/960859","article-title":"A Review of Intra- and Extracellular Antigen Delivery Systems for Virus Vaccines of Finfish","volume":"2015","author":"HM Munang\u2019andu","year":"2015","journal-title":"J Immunol Res"},{"issue":"6389","key":"pone.0310703.ref097","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1038\/358764a0","article-title":"Predominant naturally processed peptides bound to HLA-DR1 are derived from MHC-related molecules and are heterogeneous in size","volume":"358","author":"RM Chicz","year":"1992","journal-title":"Nature"},{"issue":"Suppl 4","key":"pone.0310703.ref098","doi-asserted-by":"crossref","first-page":"S395","DOI":"10.1093\/infdis\/jiz455","article-title":"Cytokine Induction in Nipah Virus-Infected Primary Human and Porcine Bronchial Epithelial Cells","volume":"221","author":"M Elvert","year":"2020","journal-title":"J Infect Dis"},{"issue":"1","key":"pone.0310703.ref099","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1146\/annurev.immunol.17.1.51","article-title":"Immunodominance in Major Histocompatibility Complex Class I\u2013Restricted T Lymphocyte Responses","volume":"17","author":"JW Yewdell","year":"1999","journal-title":"Annual Review of Immunology"},{"issue":"1","key":"pone.0310703.ref100","doi-asserted-by":"crossref","first-page":"10842","DOI":"10.1038\/s41598-024-60680-9","article-title":"Advancing molecular modeling and reverse vaccinology in broad-spectrum yellow fever virus vaccine development","volume":"14","author":"OLT da Silva","year":"2024","journal-title":"Scientific Reports"},{"issue":"Pt 2","key":"pone.0310703.ref101","doi-asserted-by":"crossref","first-page":"130754","DOI":"10.1016\/j.ijbiomac.2024.130754","article-title":"Identification of potential vaccine targets for elicitation of host immune cells against SARS-CoV-2 by reverse vaccinology approach","volume":"265","author":"S Yasmin","year":"2024","journal-title":"International Journal of Biological Macromolecules"},{"key":"pone.0310703.ref102","first-page":"1","article-title":"In-silico screening and identification of phytochemicals from Centella asiatica as potential inhibitors of sodium-glucose co-transporter 2 for treating diabetes","volume":"40","author":"MA Macalalad","year":"2021","journal-title":"Journal of Biomolecular Structure and Dynamics"},{"key":"pone.0310703.ref103","doi-asserted-by":"crossref","first-page":"108846","DOI":"10.1016\/j.jmgm.2024.108846","article-title":"The potential of Chlorella spp. as antiviral source against African swine fever virus through a virtual screening pipeline","volume":"132","author":"ANG Dulay","year":"2024","journal-title":"Journal of Molecular Graphics and Modelling"},{"issue":"3","key":"pone.0310703.ref104","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/s00251-016-0964-4","article-title":"Polymorphism at expressed DQ and DR loci in five common equine MHC haplotypes","volume":"69","author":"D Miller","year":"2017","journal-title":"Immunogenetics"},{"key":"pone.0310703.ref105","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2017.00278","article-title":"The Immune Epitope Database and Analysis Resource in Epitope Discovery and Synthetic Vaccine Design","volume":"8","author":"W Fleri","year":"2017","journal-title":"Frontiers in Immunology"},{"key":"pone.0310703.ref106","article-title":"An In Silico Multi-epitopes Vaccine Ensemble and Characterization Against Nosocomial Proteus penneri","author":"A Ullah","year":"2023","journal-title":"Molecular Biotechnology"},{"issue":"4","key":"pone.0310703.ref107","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/0923-2494(93)80102-5","article-title":"Enhancement of peptide immunogenicity by insertion of a cathepsin B cleavage site between determinants recognized by B and T cells","volume":"144","author":"P Sarobe","year":"1993","journal-title":"Research in Immunology"},{"issue":"3","key":"pone.0310703.ref108","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1111\/j.0300-9475.2004.01442.x","article-title":"Epitope DNA Vaccines Against Tuberculosis: Spacers and Ubiquitin Modulates Cellular Immune Responses Elicited by Epitope DNA Vaccine","volume":"60","author":"QM Wang","year":"2004","journal-title":"Scandinavian Journal of Immunology"},{"issue":"11","key":"pone.0310703.ref109","doi-asserted-by":"crossref","first-page":"5499","DOI":"10.4049\/jimmunol.168.11.5499","article-title":"A Rational Strategy to Design Multiepitope Immunogens Based on Multiple Th Lymphocyte Epitopes1","volume":"168","author":"B Livingston","year":"2002","journal-title":"The Journal of Immunology"},{"issue":"3","key":"pone.0310703.ref110","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/S0014-5793(98)01010-2","article-title":"Decelerated degradation of short peptides by the 20S proteasome","volume":"434","author":"I Dolenc","year":"1998","journal-title":"FEBS Letters"},{"issue":"7","key":"pone.0310703.ref111","doi-asserted-by":"crossref","first-page":"1957","DOI":"10.1002\/eji.201445329","article-title":"Mycobacterium tuberculosis RpfE promotes simultaneous Th1- and Th17-type T-cell immunity via TLR4-dependent maturation of dendritic cells","volume":"45","author":"HG Choi","year":"2015","journal-title":"European Journal of Immunology"},{"issue":"1","key":"pone.0310703.ref112","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1385\/IR:33:1:083","article-title":"Effects of flagellin on innate and adaptive immunity","volume":"33","author":"AN Honko","year":"2005","journal-title":"Immunol Res"},{"issue":"8","key":"pone.0310703.ref113","doi-asserted-by":"crossref","first-page":"e104351","DOI":"10.1371\/journal.pone.0104351","article-title":"A potential protein adjuvant derived from Mycobacterium tuberculosis Rv0652 enhances dendritic cells-based tumor immunotherapy","volume":"9","author":"SJ Lee","year":"2014","journal-title":"PLoS One"},{"issue":"1","key":"pone.0310703.ref114","doi-asserted-by":"crossref","first-page":"29373","DOI":"10.1038\/srep29373","article-title":"Phenol-soluble modulin \u03b14 mediates Staphylococcus aureus-associated vascular leakage by stimulating heparin-binding protein release from neutrophils","volume":"6","author":"L Li","year":"2016","journal-title":"Sci Rep"},{"issue":"2","key":"pone.0310703.ref115","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.molimm.2015.05.008","article-title":"Evidence for TLR4 and FcR\u03b3\u2013CARD9 activation by cholera toxin B subunit and its direct bindings to TREM2 and LMIR5 receptors","volume":"66","author":"V Phongsisay","year":"2015","journal-title":"Molecular Immunology"},{"issue":"35","key":"pone.0310703.ref116","doi-asserted-by":"crossref","first-page":"30393","DOI":"10.1074\/jbc.M111.266528","article-title":"Toll-like Receptor 4 (TLR4) Is Essential for Hsp70-like Protein 1 (HSP70L1) to Activate Dendritic Cells and Induce Th1 Response","volume":"286","author":"H Fang","year":"2011","journal-title":"J Biol Chem"},{"issue":"47","key":"pone.0310703.ref117","doi-asserted-by":"crossref","first-page":"18631","DOI":"10.1073\/pnas.0702130104","article-title":"Human \u03b2-defensin-3 activates professional antigen-presenting cells via Toll-like receptors 1 and 2","volume":"104","author":"N Funderburg","year":"2007","journal-title":"Proceedings of the National Academy of Sciences"},{"issue":"8","key":"pone.0310703.ref118","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1093\/protein\/14.8.529","article-title":"Design of the linkers which effectively separate domains of a bifunctional fusion protein","volume":"14","author":"R Arai","year":"2001","journal-title":"Protein Engineering"},{"issue":"6","key":"pone.0310703.ref119","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1016\/j.drudis.2020.03.006","article-title":"Epitope-based vaccine design: a comprehensive overview of bioinformatics approaches","volume":"25","author":"S Parvizpour","year":"2020","journal-title":"Drug Discovery Today"},{"key":"pone.0310703.ref120","doi-asserted-by":"crossref","DOI":"10.1177\/25151355221100218","article-title":"Predicting epitopes for vaccine development using bioinformatics tools","volume":"10","author":"V Yurina","year":"2022","journal-title":"Therapeutic Advances in Vaccines and Immunotherapy"},{"issue":"3","key":"pone.0310703.ref121","doi-asserted-by":"crossref","first-page":"274","DOI":"10.2174\/1573409919666230612125440","article-title":"Designing a Multi-epitope Vaccine against the SARS-CoV-2 Variant based on an Immunoinformatics Approach","volume":"20","author":"I Farhani","year":"2024","journal-title":"Current Computer-Aided Drug Design"},{"key":"pone.0310703.ref122","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/07391102.2023.2258403","article-title":"Computational design of a multi-epitope vaccine candidate against Langya henipavirus using surface proteins","author":"S Ahmad","year":"2023","journal-title":"Journal of Biomolecular Structure and Dynamics"},{"key":"pone.0310703.ref123","doi-asserted-by":"crossref","first-page":"131517","DOI":"10.1016\/j.ijbiomac.2024.131517","article-title":"In silico design of a novel multi-epitope vaccine against HCV infection through immunoinformatics approaches","volume":"267","author":"S Ahmad","year":"2024","journal-title":"International Journal of Biological Macromolecules"},{"key":"pone.0310703.ref124","first-page":"1573","article-title":"Should a Toll-like receptor 4 (TLR-4) agonist or antagonist be designed to treat cancer? TLR-4: its expression and effects in the ten most common cancers","volume":"6","author":"CW Mai","year":"2013","journal-title":"OncoTargets and Therapy"},{"issue":"8","key":"pone.0310703.ref125","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.3390\/pharmaceutics14081671","article-title":"Protein-Based Adjuvants for Vaccines as Immunomodulators of the Innate and Adaptive Immune Response: Current Knowledge, Challenges, and Future Opportunities","volume":"14","author":"DA D\u00edaz-Dinamarca","year":"2022","journal-title":"Pharmaceutics"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0310703","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,26]],"date-time":"2024-09-26T13:30:33Z","timestamp":1727357433000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0310703"}},"subtitle":[],"editor":[{"given":"Naveed","family":"Ahmed","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,9,26]]},"references-count":125,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024,9,26]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0310703","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,26]]}}}