{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T01:09:21Z","timestamp":1793149761435,"version":"4.5.0"},"reference-count":66,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,2,24]],"date-time":"2023-02-24T00:00:00Z","timestamp":1677196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"UAE University Zayed Centre-Based","award":["31R135"],"award-info":[{"award-number":["31R135"]}]},{"name":"UAE University Zayed Centre-Based","award":["31R259"],"award-info":[{"award-number":["31R259"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Epstein\u2013Barr virus (EBV) is etiologically associated with a number of malignant and non-malignant conditions. Thus, a prophylactic vaccine against this virus could help to reduce the burden of many EBV-associated diseases. Previously, we reported that an EBV virus-like particle (VLP) vaccine was highly immunogenic and produced a strong humoral response in mice. However, since EBV does not infect mice, the efficacy of the VLP in preventing EBV infection could not be addressed. Here we examined, for the first time, the efficacy of the EBV-VLP vaccine using a novel rabbit model of EBV infection. Animals vaccinated with two doses of VLP elicited higher antibody responses to total EBV antigens compared to animals receiving one dose. Vaccinated animals also elicited both IgM and IgG to EBV-specific antigens, VCA and EBNA1. Analysis of peripheral blood and spleen for EBV copy number indicated that the viral load in both of these compartments was lower in animals receiving a 2-dose vaccine. However, the VLP vaccine was ineffective in preventing EBV infection. With several other EBV vaccine candidates currently at various stages of development and testing, we believe that the rabbit model of EBV infection could be a great platform for evaluating potential candidates.<\/jats:p>","DOI":"10.3390\/vaccines11030540","type":"journal-article","created":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T03:52:21Z","timestamp":1677469941000},"page":"540","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Assessing the Efficacy of VLP-Based Vaccine against Epstein-Barr Virus Using a Rabbit Model"],"prefix":"10.3390","volume":"11","author":[{"given":"Narendran","family":"Reguraman","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asma","family":"Hassani","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pretty S.","family":"Philip","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dagmar","family":"Pich","sequence":"additional","affiliation":[{"name":"Research Unit Gene Vectors, Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health, 25, D-81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Hammerschmidt","sequence":"additional","affiliation":[{"name":"Research Unit Gene Vectors, Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health, 25, D-81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6836-1783","authenticated-orcid":false,"given":"Gulfaraz","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates"},{"name":"Zayed Center for Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/S1074-7613(00)80493-8","article-title":"Is EBV Persistence In Vivo a Model for B Cell Homeostasis?","volume":"5","author":"Khan","year":"1996","journal-title":"Immunity"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/S1074-7613(00)80622-6","article-title":"EBV Persistence in Memory B Cells In Vivo","volume":"9","author":"Babcock","year":"1998","journal-title":"Immunity"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1182\/blood-2007-06-093278","article-title":"On the Dynamics of Acute EBV Infection and the Pathogenesis of Infectious Mononucleosis","volume":"111","author":"Hadinoto","year":"2008","journal-title":"Blood"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e33","DOI":"10.1038\/cti.2015.1","article-title":"Infectious Mononucleosis","volume":"4","author":"Balfour","year":"2015","journal-title":"Clin. Transl. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2899","DOI":"10.1084\/jem.20071030","article-title":"Dysregulated Epstein-Barr Virus Infection in the Multiple Sclerosis Brain","volume":"204","author":"Serafini","year":"2007","journal-title":"J. Exp. Med."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Hassani, A., Corboy, J.R., Al-Salam, S., and Khan, G. (2018). Epstein-Barr Virus Is Present in the Brain of Most Cases of Multiple Sclerosis and May Engage More than Just B Cells. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0192109"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1126\/science.abj8222","article-title":"Longitudinal Analysis Reveals High Prevalence of Epstein-Barr Virus Associated with Multiple Sclerosis","volume":"375","author":"Bjornevik","year":"2022","journal-title":"Science"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/s41586-022-04432-7","article-title":"Clonally Expanded B Cells in Multiple Sclerosis Bind EBV EBNA1 and GlialCAM","volume":"603","author":"Lanz","year":"2022","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1097\/TP.0000000000002146","article-title":"The Changing Epidemiology of Posttransplant Lymphoproliferative Disorder in Adult Solid Organ Transplant Recipients over 30 Years: A Single-Center Experience","volume":"102","author":"Peters","year":"2018","journal-title":"Transplantation"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1056\/NEJMra1702693","article-title":"Post-Transplantation Lymphoproliferative Disorders in Adults","volume":"378","author":"Dierickx","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1038\/s41579-019-0249-7","article-title":"Latency and Lytic Replication in Epstein\u2013Barr Virus-Associated Oncogenesis","volume":"17","year":"2019","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1737","DOI":"10.7150\/jca.37282","article-title":"Epstein Barr Virus Associated Lymphomas and Epithelia Cancers in Humans","volume":"11","author":"Ayee","year":"2020","journal-title":"J. Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e037505","DOI":"10.1136\/bmjopen-2020-037505","article-title":"Global and Regional Incidence, Mortality and Disability-Adjusted Life-Years for Epstein-Barr Virus-Attributable Malignancies, 1990\u20132017","volume":"10","author":"Khan","year":"2020","journal-title":"BMJ Open"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s00432-021-03824-y","article-title":"Estimating the Global Burden of Epstein\u2013Barr Virus-Related Cancers","volume":"148","author":"Wong","year":"2021","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e124714","DOI":"10.1172\/jci.insight.124714","article-title":"Epstein-Barr Virus-Specific T Cell Therapy for Progressive Multiple Sclerosis","volume":"3","author":"Pender","year":"2018","journal-title":"JCI Insight"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4315","DOI":"10.1007\/s00018-020-03538-3","article-title":"Vaccination against the Epstein-Barr Virus","volume":"77","author":"Leung","year":"2020","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/s41390-019-0591-5","article-title":"The Promise of a Prophylactic Epstein\u2013Barr Virus Vaccine","volume":"87","author":"Balfour","year":"2020","journal-title":"Pediatr. Res."},{"key":"ref_18","first-page":"171","article-title":"First EBV Vaccine Trial in Humans Using Recombinant Vaccinia Virus Expressing the Major Membrane Antigen","volume":"84","author":"Gu","year":"1995","journal-title":"Dev. Biol. Stand."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4697","DOI":"10.1016\/j.vaccine.2007.04.008","article-title":"Phase I\/II Studies to Evaluate Safety and Immunogenicity of a Recombinant Gp350 Epstein\u2013Barr Virus Vaccine in Healthy Adults","volume":"25","author":"Moutschen","year":"2007","journal-title":"Vaccine"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1128\/JVI.01409-07","article-title":"Phase I Trial of a CD8+ T-Cell Peptide Epitope-Based Vaccine for Infectious Mononucleosis","volume":"82","author":"Elliott","year":"2008","journal-title":"J. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1097\/TP.0b013e3181b9d918","article-title":"A Phase I Trial of Epstein-Barr Virus Gp350 Vaccine for Children with Chronic Kidney Disease Awaiting Transplantation","volume":"88","author":"Rees","year":"2009","journal-title":"Transplantation"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4050","DOI":"10.1016\/j.vaccine.2016.06.021","article-title":"Rabbits Immunized with Epstein-Barr Virus GH\/GL or GB Recombinant Proteins Elicit Higher Serum Virus Neutralizing Activity than Gp350","volume":"34","author":"Cui","year":"2016","journal-title":"Vaccine"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2161","DOI":"10.1016\/S0140-6736(07)60946-5","article-title":"Efficacy of a Prophylactic Adjuvanted Bivalent L1 Virus-like-Particle Vaccine against Infection with Human Papillomavirus Types 16 and 18 in Young Women: An Interim Analysis of a Phase III Double-Blind, Randomised Controlled Trial","volume":"369","author":"Paavonen","year":"2007","journal-title":"Lancet"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.vaccine.2012.10.083","article-title":"Virus-like Particles as a Highly Efficient Vaccine Platform: Diversity of Targets and Production Systems and Advances in Clinical Development","volume":"31","author":"Kushnir","year":"2012","journal-title":"Vaccine"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"13105","DOI":"10.1128\/JVI.05598-11","article-title":"A Virus-like Particle-Based Epstein-Barr Virus Vaccine","volume":"85","author":"Ruiss","year":"2011","journal-title":"J. Virol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1515\/jbcpp-2018-0002","article-title":"Rabbits and Men: Relating Their Ages","volume":"29","author":"Dutta","year":"2018","journal-title":"J. Basic Clin. Physiol. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s12985-015-0260-1","article-title":"Healthy Rabbits Are Susceptible to Epstein-Barr Virus Infection and Infected Cells Proliferate in Immunosuppressed Animals","volume":"12","author":"Khan","year":"2015","journal-title":"Virol. J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5188","DOI":"10.1073\/pnas.96.9.5188","article-title":"A First-Generation Packaging Cell Line for Epstein\u2013Barr Virus-Derived Vectors","volume":"96","author":"Delecluse","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Albanese, M., Chen, Y.-F.A., H\u00fcls, C., G\u00e4rtner, K., Tagawa, T., Mejias-Perez, E., Keppler, O.T., G\u00f6bel, C., Zeidler, R., and Shein, M. (2021). MicroRNAs Are Minor Constituents of Extracellular Vesicles That Are Rarely Delivered to Target Cells. PLoS Genet., 17.","DOI":"10.1371\/journal.pgen.1009951"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"16286","DOI":"10.1073\/pnas.0407320101","article-title":"Proteins of Purified Epstein-Barr Virus","volume":"101","author":"Johannsen","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"14326","DOI":"10.1128\/JVI.01691-14","article-title":"Expression of the Human Cytomegalovirus UL11 Glycoprotein in Viral Infection and Evaluation of Its Effect on Virus-Specific CD8 T Cells","volume":"88","author":"Gabaev","year":"2014","journal-title":"J. Virol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1038\/sj.gt.3302714","article-title":"Genetic Design of an Optimized Packaging Cell Line for Gene Vectors Transducing Human B Cells","volume":"13","author":"Hettich","year":"2006","journal-title":"Gene Ther."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/S1525-1578(10)60535-1","article-title":"Epstein-Barr Virus Quantitation by Real-Time PCR Targeting Multiple Gene Segments","volume":"6","author":"Ryan","year":"2004","journal-title":"J. Mol. Diagn."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1136\/jcp.45.7.616","article-title":"Epstein Barr Virus (EBV) Encoded Small RNAs: Targets for Detection by In Situ Hybridisation with Oligonucleotide Probes","volume":"45","author":"Khan","year":"1992","journal-title":"J. Clin. Pathol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1007\/978-1-59745-447-6_13","article-title":"Screening for Epstein-Barr Virus in Hodgkin\u2019s Lymphoma","volume":"511","author":"Khan","year":"2009","journal-title":"Methods Mol. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1016\/S0140-6736(64)91524-7","article-title":"Virus Particles in Cultured Lymphoblasts from Burkitt\u2019s Lymphoma","volume":"1","author":"Epstein","year":"1964","journal-title":"Lancet"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1146\/annurev.mi.27.100173.002213","article-title":"The EB Virus","volume":"27","author":"Epstein","year":"1973","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1038\/nrc.2016.92","article-title":"Epstein-Barr Virus: More than 50 Years Old and Still Providing Surprises","volume":"16","author":"Young","year":"2017","journal-title":"Nat. Rev. Cancer"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"107fs7","DOI":"10.1126\/scitranslmed.3002878","article-title":"Epstein-Barr Virus: An Important Vaccine Target for Cancer Prevention","volume":"3","author":"Cohen","year":"2011","journal-title":"Sci. Transl. Med."},{"key":"ref_40","first-page":"989","article-title":"Relation between Neutralization of Epstein-Barr Virus and Antibodies to Cell-Membrane Antigens Induced by the Virus","volume":"45","author":"Pearson","year":"1970","journal-title":"JNCI J. Natl. Cancer Inst."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1016\/S0264-410X(98)00248-5","article-title":"Expression of Epstein\u2013Barr Virus Gp350 as a Single Chain Glycoprotein for an EBV Subunit Vaccine","volume":"17","author":"Jackman","year":"1999","journal-title":"Vaccine"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1084\/jem.171.1.345","article-title":"An Epstein-Barr Virus-Specific Cytotoxic T Cell Epitope in EBV Nuclear Antigen 3 (EBNA 3)","volume":"171","author":"Burrows","year":"1990","journal-title":"J. Exp. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1084\/jem.176.1.169","article-title":"Localization of Epstein-Barr Virus Cytotoxic T Cell Epitopes Using Recombinant Vaccinia: Implications for Vaccine Development","volume":"176","author":"Khanna","year":"1992","journal-title":"J. Exp. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3039","DOI":"10.1016\/j.vaccine.2013.04.071","article-title":"A Novel Tetrameric Gp3501-470 as a Potential Epstein-Barr Virus Vaccine","volume":"31","author":"Cui","year":"2013","journal-title":"Vaccine"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"7825","DOI":"10.1128\/JVI.00445-07","article-title":"Epstein-Barr Virus Entry","volume":"81","year":"2007","journal-title":"J. Virol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1676","DOI":"10.1158\/0008-5472.CAN-12-2448","article-title":"Phase 1 Trial of Recombinant Modified Vaccinia Ankara (MVA) Encoding Epstein-Barr Viral Tumor Antigens in Nasopharyngeal Carcinoma Patients","volume":"73","author":"Hui","year":"2013","journal-title":"Cancer Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1016\/j.cell.2015.07.043","article-title":"Rational Design of an Epstein-Barr Virus Vaccine Targeting the Receptor-Binding Site","volume":"162","author":"Kanekiyo","year":"2015","journal-title":"Cell"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/j.immuni.2018.03.026","article-title":"An Antibody Targeting the Fusion Machinery Neutralizes Dual-Tropic Infection and Defines a Site of Vulnerability on Epstein-Barr Virus","volume":"48","author":"Snijder","year":"2018","journal-title":"Immunity"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"6624","DOI":"10.1038\/s41467-021-26912-6","article-title":"A Potent and Protective Human Neutralizing Antibody Targeting a Novel Vulnerable Site of Epstein-Barr Virus","volume":"12","author":"Zhu","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Escalante, G.M., Foley, J., Mutsvunguma, L.Z., Rodriguez, E., Mulama, D.H., Muniraju, M., Ye, P., Barasa, A.K., and Ogembo, J.G. (2020). A Pentavalent Epstein-Barr Virus-Like Particle Vaccine Elicits High Titers of Neutralizing Antibodies against Epstein-Barr Virus Infection in Immunized Rabbits. Vaccines, 8.","DOI":"10.3390\/vaccines8020169"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2011","DOI":"10.1128\/JVI.02533-12","article-title":"An Epstein-Barr Virus Mutant Produces Immunogenic Defective Particles Devoid of Viral DNA","volume":"87","author":"Pavlova","year":"2013","journal-title":"J. Virol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"van Zyl, D.G., Tsai, M.-H., Shumilov, A., Schneidt, V., Poirey, R., Schlehe, B., Fluhr, H., Mautner, J., and Delecluse, H.-J. (2018). Immunogenic Particles with a Broad Antigenic Spectrum Stimulate Cytolytic T Cells and Offer Increased Protection against EBV Infection Ex Vivo and in Mice. PLoS Pathog., 14.","DOI":"10.1371\/journal.ppat.1007464"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s12967-015-0415-2","article-title":"A Chimeric EBV Gp350\/220-Based VLP Replicates the Virion B-Cell Attachment Mechanism and Elicits Long-Lasting Neutralizing Antibodies in Mice","volume":"13","author":"Ogembo","year":"2015","journal-title":"J. Transl. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"104","DOI":"10.3389\/fonc.2019.00104","article-title":"Progress in EBV Vaccines","volume":"9","author":"Mautner","year":"2019","journal-title":"Front. Oncol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"19255","DOI":"10.18632\/oncotarget.13770","article-title":"Novel Epstein-Barr Virus-like Particles Incorporating GH\/GL-EBNA1 or GB-LMP2 Induce High Neutralizing Antibody Titers and EBV-Specific T-Cell Responses in Immunized Mice","volume":"8","author":"Perez","year":"2017","journal-title":"Oncotarget"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"eabf3685","DOI":"10.1126\/scitranslmed.abf3685","article-title":"A Bivalent Epstein-Barr Virus Vaccine Induces Neutralizing Antibodies That Block Infection and Confer Immunity in Humanized Mice","volume":"14","author":"Wei","year":"2022","journal-title":"Sci. Transl. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e00336-22","DOI":"10.1128\/jvi.00336-22","article-title":"Vesicular Stomatitis Virus-Based Epstein-Barr Virus Vaccines Elicit Strong Protective Immune Responses","volume":"96","author":"Kong","year":"2022","journal-title":"J. Virol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.virusres.2010.07.026","article-title":"Lifelong Persistent EBV Infection of Rabbits with EBER1-Positive Lymphocyte Infiltration and Mild Sublethal Hemophagocytosis","volume":"153","author":"Kanai","year":"2010","journal-title":"Virus Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1002\/jmv.21597","article-title":"Epstein-Barr Virus Can Infect Rabbits by the Intranasal or Peroral Route: An Animal Model for Natural Primary EBV Infection in Humans","volume":"82","author":"Okuno","year":"2010","journal-title":"J. Med. Virol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"312","DOI":"10.30802\/AALAS-CM-20-000019","article-title":"Antibody-Mediated Immune Subset Depletion Modulates the Immune Response in a Rabbit (Oryctolagus Cuniculus) Model of Epstein-Barr Virus Infection","volume":"70","author":"Osborne","year":"2020","journal-title":"Comp. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jmv.21102","article-title":"A New Animal Model for Primary and Persistent Epstein-Barr Virus Infection: Human EBV-Infected Rabbit Characteristics Determined Using Sequential Imaging and Pathological Analysis","volume":"80","author":"Takashima","year":"2008","journal-title":"J. Med. Virol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"6372","DOI":"10.4049\/jimmunol.171.12.6372","article-title":"B Lymphocyte Development in Rabbit: Progenitor B Cells and Waning of B Lymphopoiesis","volume":"171","author":"Jasper","year":"2003","journal-title":"J. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2119","DOI":"10.1084\/jem.183.5.2119","article-title":"Evidence for Limited B-Lymphopoiesis in Adult Rabbits","volume":"183","author":"Crane","year":"1996","journal-title":"J. Exp. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.clim.2017.08.004","article-title":"Adjuvant Formulations for Virus-like Particle (VLP) Based Vaccines","volume":"183","author":"Cimica","year":"2017","journal-title":"Clin. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1159\/000343753","article-title":"EBNA-2 -Deleted Epstein-Barr Virus from P3HR-1 Can Infect Rabbits with Lower Efficiency than Prototype Epstein-Barr Virus from B95-8","volume":"56","author":"Sano","year":"2013","journal-title":"Intervirology"},{"key":"ref_66","unstructured":"Priyan, V. (2023, February 02). Moderna Doses First Subject in Phase I EBV Vaccine Trial. Available online: https:\/\/www.clinicaltrialsarena.com\/news\/moderna-ebv-vaccine-trial\/."}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/11\/3\/540\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:41:50Z","timestamp":1760121710000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/11\/3\/540"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,24]]},"references-count":66,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["vaccines11030540"],"URL":"https:\/\/doi.org\/10.3390\/vaccines11030540","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,24]]}}}