{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:17:14Z","timestamp":1787062634586,"version":"build-2736575974"},"reference-count":61,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T00:00:00Z","timestamp":1740614400000},"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>Introduction<\/jats:title>\n                    <jats:p>The Zika virus is an emerging Flavivirus known to cause Zika infection in humans. It is associated with severe health problems such as microcephaly and Guillain-Barr\u00e9 syndrome post the Brazilian epidemic in 2015-16. The spread of the Zika virus to the Asian subcontinent, especially to India is a matter of great concern. Two recent co-circulating Indian Zika virus strains such as Rajasthan and Maharashtra detected in 2018 and 2021 were studied to identify B-cell epitopes in the envelope and non-structural 1 protein as these epitopes are major indicators of robust humoral immune response. The study aimed at identifying novel epitopes, followed by molecular docking with potent Zika virus-specific monoclonal antibodies. The novel epitopes identified in this study shall be essential in designing multi-epitope vaccines capable of inducing antibody response against Zika virus infection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>ABCpred, BepiPred 2.0 and Kolaskar-Tongaonkar methods were used for predicting the linear B-cell epitopes, and Discotope 2.0 and ElliPro were used for the prediction of conformational epitopes. Linear epitopes were further checked for protective antigenicity, allergenicity and toxicity. Based on the stringent study design criteria, only the novel epitopes were considered for molecular docking with complementary determining regions of potent Zika virus-specific monoclonal antibodies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Nineteen linear and five conformational epitopes were shortlisted based on protective potential, non-allergic and non-toxic properties for Zika virus E protein, from which nine linear and three conformational epitopes were identified as novel. Molecular docking studies revealed that the novel linear epitopes, one each from EDIII, EDII, EDI and EDI\/DIII hinge were involved in epitope-CDR interactions with potent neutralizing Zika virus E-specific mouse monoclonal antibody ZV-67. Moreover, the novel EDII epitope was exclusively engaged in epitope-CDR interactions of potent neutralizing Zika virus E-specific human monoclonal antibody Z3L1. None of the linear epitopes of Zika virus NS1 were ascertained as novel based on our study criteria. Conformational epitopes were identified as novel for NS1 protein.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This study identified Zika virus-specific novel epitopes of envelope and non-structural -1 proteins in the currently co-circulating Indian strains. Furthermore, in-silico validation through molecular docking added insight into antigen-antibody interactions, paving way for future\n                      <jats:italic>in vitro<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      studies.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1534737","type":"journal-article","created":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T02:03:00Z","timestamp":1740621780000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Identification of B-cell epitopes of Indian Zika virus strains using immunoinformatics"],"prefix":"10.3389","volume":"16","author":[{"given":"Rohan Raj","family":"Roy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nitali","family":"Tadkalkar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gururaj Rao","family":"Deshpande","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nitin M.","family":"Atre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pratip","family":"Shil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gajanan","family":"Sapkal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,2,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/0035-9203(52)90042-4","article-title":"Zika Virus (I). Isolations and serological specificity","volume":"46","author":"Dick","year":"1952","journal-title":"Trans R Soc Trop Med Hyg"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0805715","article-title":"Zika virus outbreak on yap island, federated states of Micronesia","volume":"360","author":"Duffy","year":"2009","journal-title":"New Engl J Med"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1126\/science.aam7120","article-title":"A single mutation in the prM protein of Zika virus contributes to fetal microcephaly","volume":"358","author":"Yuan","year":"2017","journal-title":"Sci (1979)"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1608612","article-title":"Zika virus infection and associated neurologic disorders in Brazil","volume":"376","author":"de Oliveira","year":"2017","journal-title":"New Engl J Med"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)00562-6","article-title":"Guillain-Barr\u00e9 Syndrome outbreak associated with Zika virus infection in French Polynesia: a case-control study","volume":"387","author":"Cao-Lormeau","year":"2016","journal-title":"Lancet"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3855\/jidc.8217","article-title":"Zika virus outbreak in Brazil","volume":"10","author":"Heukelbach","year":"2016","journal-title":"J Infection Developing Countries"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1590\/0074-02760150192","article-title":"First report of autochthonous transmission of Zika virus in Brazil","volume":"110","author":"Zanluca","year":"2015","journal-title":"Mem Inst Oswaldo Cruz"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2017.09.020","article-title":"First laboratory confirmation on the existence of Zika virus disease in India","volume":"76","author":"Sapkal","year":"2018","journal-title":"J Infection"},{"key":"B9","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.meegid.2019.01.026","article-title":"Zika virus outbreak in Rajasthan, India in 2018 was caused by a virus endemic to Asia","volume":"69","author":"Yadav","year":"2019","journal-title":"Infection Genet Evolution"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.jiph.2020.10.006","article-title":"Clinico-epidemiological and genomic profile of first Zika Virus outbreak in India at Jaipur city of Rajasthan state","volume":"13","author":"Malhotra","year":"2020","journal-title":"J Infect Public Health"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1093\/trstmh\/trac022","article-title":"First case of Zika virus infection during an outbreak of chikungunya in a rural region of Maharashtra state, India","volume":"116","author":"Gurav","year":"2022","journal-title":"Trans R Soc Trop Med Hyg"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1097\/MOP.0000000000000441","article-title":"Potential for treatment and a Zika virus vaccine","volume":"29","author":"Quanquin","year":"2017","journal-title":"Curr Opin Pediatr"},{"key":"B13","doi-asserted-by":"publisher","first-page":"e0004530","DOI":"10.1371\/journal.pntd.0004530","article-title":"Zika virus: medical countermeasure development challenges","volume":"10","author":"Malone","year":"2016","journal-title":"PloS Negl Trop Dis"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm6533e2","article-title":"Update: interim guidance for the evaluation and management of infants with possible congenital zika virus infection \u2014 United states, august 2016","volume":"65","author":"Russell","year":"2016","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jix513","article-title":"Humoral immune responses against zika virus infection and the importance of preexisting flavivirus immunity","volume":"216","author":"Priyamvada","year":"2017","journal-title":"J Infect Dis"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2020.1816493","article-title":"Design of a multi-epitope peptide vaccine candidate against chandipura virus: an immuno-informatics study","volume":"40","author":"Pavitrakar","year":"2022","journal-title":"J Biomol Struct Dyn"},{"key":"B17","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.virusres.2011.08.008","article-title":"Induction of virus-specific neutralizing immune response against West Nile and Japanese encephalitis viruses by chimeric peptides representing T-helper and B-cell epitopes","volume":"163","author":"Gangwar","year":"2012","journal-title":"Virus Res"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2013.00302","article-title":"The structural basis of antibody-antigen recognition","volume":"4","author":"Sela-Culang","year":"2013","journal-title":"Front Immunol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1007\/s12250-019-00093-5","article-title":"Development of neutralizing antibodies against zika virus based on its envelope protein structure","volume":"34","author":"Yang","year":"2019","journal-title":"Virol Sin"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01485-19","article-title":"Role of zika virus envelope protein domain III as a target of human neutralizing antibodies","volume":"10","author":"Gallichotte","year":"2019","journal-title":"mBio"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf8505","article-title":"Specificity, cross-reactivity, and function of antibodies elicited by Zika virus infection","volume":"353","author":"Stettler","year":"2016","journal-title":"Science"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201695871","article-title":"Zika virus NS 1, a pathogenicity factor with many faces","volume":"35","author":"Hilgenfeld","year":"2016","journal-title":"EMBO J"},{"key":"B23","doi-asserted-by":"publisher","first-page":"4560","DOI":"10.1038\/s41467-018-07008-0","article-title":"Human antibodies targeting Zika virus NS1 provide protection against disease in a mouse model","volume":"9","author":"Bailey","year":"2018","journal-title":"Nat Commun"},{"key":"B24","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.03179-20","article-title":"Monoclonal Antibodies against Zika Virus NS1 Protein Confer Protection via Fc \u03b3 Receptor-Dependent and -Independent Pathways","volume":"12","author":"Yu","year":"2021","journal-title":"mBio"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.3268","article-title":"Extended surface for membrane association in Zika virus NS1 structure","volume":"23","author":"Brown","year":"2016","journal-title":"Nat Struct Mol Biol"},{"key":"B26","first-page":"77","article-title":"Structures of zika virus E & NS1: relations with virus infection and host immune responses","author":"Shi","year":"2018"},{"key":"B27","doi-asserted-by":"crossref","DOI":"10.1007\/978-1-0716-3239-0_28","article-title":"Immunoinformatics vaccine design for zika virus","author":"Antonelli","year":"2023"},{"key":"B28","doi-asserted-by":"publisher","first-page":"226","DOI":"10.3390\/microorganisms7080226","article-title":"Peptide-based subunit vaccine design of T- and B-cells multi-epitopes against zika virus using immunoinformatics approaches","volume":"7","author":"Prasasty","year":"2019","journal-title":"Microorganisms"},{"key":"B29","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":"B30","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkx346","article-title":"BepiPred-2.0: improving sequence-based B-cell epitope prediction using conformational epitopes","volume":"45","author":"Jespersen","year":"2017","journal-title":"Nucleic Acids Res"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(90)80535-Q","article-title":"A semi-empirical method for prediction of antigenic determinants on protein antigens","volume":"276","author":"Kolaskar","year":"1990","journal-title":"FEBS Lett"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1002\/prot.21078","article-title":"Prediction of continuous B-cell epitopes in an antigen using recurrent neural network","volume":"65","author":"Saha","year":"2006","journal-title":"Proteins: Structure Function Bioinf"},{"key":"B33","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1533\/9781908818416.87","article-title":"Computational B cell vaccine design","author":"Tong","year":"2013","journal-title":"In: Computer-Aided Vaccine Design. Elsevier;"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.55.3.836-839.1985","article-title":"Induction of hepatitis A virus-neutralizing antibody by a virus-specific synthetic peptide","volume":"55","author":"Emini","year":"1985","journal-title":"J Virol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"2278","DOI":"10.1007\/s00894-014-2278-5","article-title":"AllerTOP v.2\u2014a server for in silico prediction of allergens","volume":"20","author":"Dimitrov","year":"2014","journal-title":"J Mol Model"},{"key":"B36","doi-asserted-by":"publisher","first-page":"e73957","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":"B37","article-title":"Peptide toxicity prediction","author":"Gupta","year":"2015","journal-title":"In"},{"key":"B38","doi-asserted-by":"publisher","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":"Ponomarenko","year":"2008","journal-title":"BMC Bioinf"},{"key":"B39","doi-asserted-by":"publisher","first-page":"e1002829","DOI":"10.1371\/journal.pcbi.1002829","article-title":"Reliable B cell epitope predictions: impacts of method development and improved benchmarking","volume":"8","author":"Kringelum","year":"2012","journal-title":"PloS Comput Biol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.07.020","article-title":"Structural basis of zika virus-specific antibody protection","volume":"166","author":"Zhao","year":"2016","journal-title":"Cell"},{"key":"B41","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1016\/j.chom.2016.04.013","article-title":"Structures of\u00a0the\u00a0zika virus envelope protein and its complex with a flavivirus broadly protective\u00a0antibody","volume":"19","author":"Dai","year":"2016","journal-title":"Cell Host Microbe"},{"key":"B42","doi-asserted-by":"publisher","first-page":"5278","DOI":"10.1038\/s41467-020-19096-y","article-title":"Antibodies targeting epitopes on the cell-surface form of NS1 protect against Zika virus infection during pregnancy","volume":"11","author":"Wessel","year":"2020","journal-title":"Nat Commun"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aai8336","article-title":"Molecular determinants of human neutralizing antibodies isolated from a patient infected with Zika virus","volume":"8","author":"Wang","year":"2016","journal-title":"Sci Transl Med"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.124588","article-title":"Human antibody response to Zika targets type-specific quaternary structure epitopes","volume":"4","author":"Collins","year":"2019","journal-title":"JCI Insight"},{"key":"B45","doi-asserted-by":"publisher","first-page":"e0292451","DOI":"10.1371\/journal.pone.0292451","article-title":"Linear epitope mapping in the E and NS1 proteins of dengue and Zika viruses: Prospection of peptides for vaccines and diagnostics","volume":"18","author":"Aquino","year":"2023","journal-title":"PloS One"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.2165\/00063030-200721030-00002","article-title":"Epitope mapping","volume":"21","author":"Gershoni","year":"2007","journal-title":"BioDrugs"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-08-100736-5.00012-0","article-title":"Peptide-based vaccines","author":"Nevagi","year":"2018","journal-title":"Pept Appl Biomedicine Biotechnol Bioengineering"},{"key":"B48","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1007\/s10989-022-10486-y","article-title":"Prediction of conformational and linear B-cell epitopes on envelop protein of zika virus using immunoinformatics approach","volume":"29","author":"Srivastava","year":"2023","journal-title":"Int J Pept Res Ther"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.00879-22","article-title":"Pathogenicity and structural basis of zika variants with glycan loop deletions in the envelope protein","volume":"96","author":"Cheng","year":"2022","journal-title":"J Virol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1515\/bmc.2010.022","article-title":"A fresh look at the Ramachandran plot and the occurrence of standard structures in proteins","volume":"1","author":"Hollingsworth","year":"2010","journal-title":"Biomol Concepts"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1080\/19420862.2023.2268255","article-title":"A window into the human immune system: comprehensive characterization of the complexity of antibody complementary-determining regions in functional antibodies","volume":"15","author":"Mejias-Gomez","year":"2023","journal-title":"MAbs"},{"key":"B52","doi-asserted-by":"publisher","first-page":"1624","DOI":"10.12688\/f1000research","article-title":"Large-scale analysis of B-cell epitopes of envelope: Implications for Zika vaccine and immunotherapeutic development","volume":"7","author":"Almansour","year":"2019","journal-title":"F1000Res"},{"key":"B53","doi-asserted-by":"publisher","first-page":"14722","DOI":"10.1038\/ncomms14722","article-title":"A human antibody against Zika virus crosslinks the E protein to prevent infection","volume":"8","author":"Hasan","year":"2017","journal-title":"Nat Commun"},{"key":"B54","doi-asserted-by":"publisher","first-page":"105915","DOI":"10.1016\/j.antiviral.2024.105915","article-title":"Structural biology of flavivirus NS1 protein and its antibody complexes","volume":"227","author":"Alvin Chew","year":"2024","journal-title":"Antiviral Res"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1101\/2023.10.16.562450","article-title":"Structural insights into the distinct protective mechanisms of human antibodies targeting ZIKV NS1","author":"Pan","year":"2024","journal-title":"hLife"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20210580","article-title":"The immunodominant antibody response to Zika virus NS1 protein is characterized by cross-reactivity to self","volume":"218","author":"Cavazzoni","year":"2021","journal-title":"J Exp Med"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1021\/bi00367a013","article-title":"New hydrophilicity scale derived from high-performance liquid chromatography peptide retention data: correlation of predicted surface residues with antigenicity and x-ray-derived accessible sites","volume":"25","author":"Parker","year":"1986","journal-title":"Biochemistry"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-020-0312-x","article-title":"The HDOCK server for integrated protein\u2013protein docking","volume":"15","author":"Yan","year":"2020","journal-title":"Nat Protoc"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1126\/science.1247749","article-title":"Flavivirus NS1 structures reveal surfaces for associations with membranes and the immune system","volume":"343","author":"Akey","year":"2014","journal-title":"Sci (1979)"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaa3863","article-title":"Dengue virus NS1 protein activates cells via Toll-like receptor 4 and disrupts endothelial cell monolayer integrity","volume":"7","author":"Modhiran","year":"2015","journal-title":"Sci Transl Med"},{"key":"B61","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1186\/s12879-018-3173-y","article-title":"Delayed and highly specific antibody response to nonstructural protein 1 (NS1) revealed during natural human ZIKV infection by NS1-based capture ELISA","volume":"18","author":"Gao","year":"2018","journal-title":"BMC Infect Dis"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1534737\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T02:03:12Z","timestamp":1740621792000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1534737\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,27]]},"references-count":61,"alternative-id":["10.3389\/fimmu.2025.1534737"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1534737","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,27]]},"article-number":"1534737"}}