{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:15:14Z","timestamp":1787030114859,"version":"build-2736575974"},"reference-count":19,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,31]],"date-time":"2022-12-31T00:00:00Z","timestamp":1672444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Centre for the Replacement, Refinement &amp; Reduction of Animals in Research (NC3Rs)","award":["NC\/R001138\/1"],"award-info":[{"award-number":["NC\/R001138\/1"]}]},{"name":"National Centre for the Replacement, Refinement &amp; Reduction of Animals in Research (NC3Rs)","award":["BBS\/E\/I\/00001845"],"award-info":[{"award-number":["BBS\/E\/I\/00001845"]}]},{"name":"National Centre for the Replacement, Refinement &amp; Reduction of Animals in Research (NC3Rs)","award":["BBS\/E\/I\/00007031"],"award-info":[{"award-number":["BBS\/E\/I\/00007031"]}]},{"name":"National Centre for the Replacement, Refinement &amp; Reduction of Animals in Research (NC3Rs)","award":["BBS\/E\/I\/00007038"],"award-info":[{"award-number":["BBS\/E\/I\/00007038"]}]},{"DOI":"10.13039\/501100000268","name":"BBSRC","doi-asserted-by":"publisher","award":["NC\/R001138\/1"],"award-info":[{"award-number":["NC\/R001138\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"BBSRC","doi-asserted-by":"publisher","award":["BBS\/E\/I\/00001845"],"award-info":[{"award-number":["BBS\/E\/I\/00001845"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"BBSRC","doi-asserted-by":"publisher","award":["BBS\/E\/I\/00007031"],"award-info":[{"award-number":["BBS\/E\/I\/00007031"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"BBSRC","doi-asserted-by":"publisher","award":["BBS\/E\/I\/00007038"],"award-info":[{"award-number":["BBS\/E\/I\/00007038"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Infectious bursal disease virus (IBDV) vaccines do not induce sterilizing immunity, and vaccinated birds can become infected with field strains. Vaccine-induced immune selection pressure drives the evolution of antigenic drift variants that accumulate amino acid changes in the hypervariable region (HVR) of the VP2 capsid, which may lead to vaccine failures. However, there is a lack of information regarding how quickly mutations arise, and the relative contribution different residues make to immune escape. To model IBDV antigenic drift in vitro, we serially passaged a classical field strain belonging to genogroup A1 (F52\/70) ten times, in triplicate, in the immortalized chicken B cell line, DT40, in the presence of sub-neutralizing concentrations of sera from birds inoculated with IBDV vaccine strain 2512, to generate escape mutants. This assay simulated a situation where classical strains may infect birds that have suboptimal vaccine-induced antibody responses. We then sequenced the HVR of the VP2 capsid at passage (P) 5 and 10 and compared the sequences to the parental virus (P0), and to the virus passaged in the presence of negative control chicken serum that lacked IBDV antibodies. Two escape mutants at P10 had the same mutations, D279Y and G281R, and a third had mutations S251I and D279N. Furthermore, at P5, the D279Y mutation was detectable, but the G281R mutation was not, indicating the mutations arose with different kinetics.<\/jats:p>","DOI":"10.3390\/v15010130","type":"journal-article","created":{"date-parts":[[2023,1,2]],"date-time":"2023-01-02T02:23:06Z","timestamp":1672626186000},"page":"130","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Modeling Infectious Bursal Disease Virus (IBDV) Antigenic Drift In Vitro"],"prefix":"10.3390","volume":"15","author":[{"given":"Amin S.","family":"Asfor","sequence":"first","affiliation":[{"name":"Birnaviruses Group, The Pirbright Institute, Ash Road, Woking GU24 0NF, UK"},{"name":"Department of Comparative Biomedical Sciences, Section Infection and Immunity, School of Veterinary Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guilford GU2 7AL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishwanatha R. A. P.","family":"Reddy","sequence":"additional","affiliation":[{"name":"Birnaviruses Group, The Pirbright Institute, Ash Road, Woking GU24 0NF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2837-3365","authenticated-orcid":false,"given":"Salik","family":"Nazki","sequence":"additional","affiliation":[{"name":"Birnaviruses Group, The Pirbright Institute, Ash Road, Woking GU24 0NF, UK"},{"name":"Pandemic Sciences Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7DQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7186-9366","authenticated-orcid":false,"given":"Joanna","family":"Urbaniec","sequence":"additional","affiliation":[{"name":"Birnaviruses Group, The Pirbright Institute, Ash Road, Woking GU24 0NF, UK"},{"name":"Department of Comparative Biomedical Sciences, Section Infection and Immunity, School of Veterinary Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guilford GU2 7AL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"Brodrick","sequence":"additional","affiliation":[{"name":"Department of Animal and Avian Sciences, College of Agriculture and Natural Resources, University of Maryland, College Park, MD 20742, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4716-1835","authenticated-orcid":false,"given":"Andrew J.","family":"Broadbent","sequence":"additional","affiliation":[{"name":"Birnaviruses Group, The Pirbright Institute, Ash Road, Woking GU24 0NF, UK"},{"name":"Department of Animal and Avian Sciences, College of Agriculture and Natural Resources, University of Maryland, College Park, MD 20742, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,31]]},"reference":[{"key":"ref_1","unstructured":"Swayne, D. (2020). Infectious Bursal Disease Virus. Diseases of Poultry, John Wiley & Sons, Inc. [14th ed.]."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"12827","DOI":"10.1128\/JVI.01501-07","article-title":"Molecular and structural bases for the antigenicity of VP2 of infectious bursal disease virus","volume":"81","author":"Letzel","year":"2007","journal-title":"J. Virol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2854","DOI":"10.1128\/JVI.73.4.2854-2862.1999","article-title":"Adaptation of very virulent infectious bursal disease virus to chicken embryonic fibroblasts by site-directed mutagenesis of residues 279 and 284 of viral coat protein VP2","volume":"73","author":"Lim","year":"1999","journal-title":"J. Virol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2067","DOI":"10.1099\/0022-1317-80-8-2067","article-title":"Tissue culture infectivity of different strains of infectious bursal disease virus is determined by distinct amino acids in VP2","volume":"80","author":"Mundt","year":"1999","journal-title":"J. Gen. Virol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1099\/0022-1317-83-1-121","article-title":"Alteration of amino acids in VP2 of very virulent infectious bursal disease virus results in tissue culture adaptation and attenuation in chickens","volume":"83","author":"Zeyda","year":"2002","journal-title":"J. Gen. Virol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1080\/03079457.2012.661403","article-title":"Current status of vaccines against infectious bursal disease","volume":"41","author":"Muller","year":"2012","journal-title":"Avian Pathol."},{"key":"ref_7","first-page":"22588","article-title":"Vaccine Failure in Poultry Production and its Control Methods: A Review","volume":"29","author":"Birhane","year":"2020","journal-title":"Biomed. J. Sci. Tech. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e02107-19","DOI":"10.1128\/JVI.02107-19","article-title":"Discrete Virus Factories Form in the Cytoplasm of Cells Coinfected with Two Replication-Competent Tagged Reporter Birnaviruses That Subsequently Coalesce over Time","volume":"94","author":"Campbell","year":"2020","journal-title":"J. Virol."},{"key":"ref_9","unstructured":"Pirbright (2022, August 12). The UK Immunological Toolbox. Available online: https:\/\/www.immunologicaltoolbox.co.uk\/search?query=ibdv."},{"key":"ref_10","unstructured":"Wark, K.L. (2000). Expression and Processing of Infectious Bursal Disease Virus Proteins, University of Hertfordshire, EThOS."},{"key":"ref_11","first-page":"494","article-title":"A simple method of estimating fifty percent endpoints","volume":"27","author":"Reed","year":"1938","journal-title":"Am. J. Hyg."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3661","DOI":"10.1007\/s00705-017-3500-4","article-title":"Classification of infectious bursal disease virus into genogroups","volume":"162","author":"Michel","year":"2017","journal-title":"Arch. Virol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1093\/molbev\/msw054","article-title":"MEGA7: Molecular Evolutionary Genetics Analysis Version 7.0 for Bigger Datasets","volume":"33","author":"Kumar","year":"2016","journal-title":"Mol. Biol. Evol."},{"key":"ref_14","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":"Jumper","year":"2021","journal-title":"Nature"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1099\/vir.0.008870-0","article-title":"Infectious bursal disease virus persistently infects bursal B-lymphoid DT40 cells","volume":"90","author":"Delgui","year":"2009","journal-title":"J. Gen. Virol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e0125522","DOI":"10.1128\/jvi.01255-22","article-title":"Evaluating the Breadth of Neutralizing Antibody Responses Elicited by Infectious Bursal Disease Virus Genogroup A1 Strains Using a Novel Chicken B-Cell Rescue System and Neutralization Assay","volume":"96","author":"Reddy","year":"2022","journal-title":"J. Virol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1292\/jvms.70.407","article-title":"Chicken B lymphoma DT40 cells as a useful tool for in vitro analysis of pathogenic infectious bursal disease virus","volume":"70","author":"Terasaki","year":"2008","journal-title":"J. Vet. Med. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/0042-6822(87)90180-2","article-title":"Deletion mapping and expression in Escherichia coli of the large genomic segment of a birnavirus","volume":"161","author":"Azad","year":"1987","journal-title":"Virology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/j.jiph.2018.12.012","article-title":"Phylogenetic analysis of Infectious Bursal Disease viruses according to newly proposed model of classification into geno-groups","volume":"12","author":"Habib","year":"2019","journal-title":"J. Infect. 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