{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T15:32:13Z","timestamp":1787671933601,"version":"build-2736575974"},"reference-count":63,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Key Research and Development Program of China","award":["2024YFC2309801"],"award-info":[{"award-number":["2024YFC2309801"]}]},{"name":"the Bagui Scholars Program of Guangxi Zhuang Autonomous Region"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background\/Objectives: Epstein\u2013Barr virus (EBV) is a ubiquitous pathogen responsible for significant malignancies and autoimmune diseases, yet no prophylactic vaccine is available. The viral entry glycoproteins gL\/gH and gB are essential for infection, but soluble forms are poorly immunogenic and fail to elicit durable neutralizing antibodies. Moreover, EBV infects both B cells and epithelial cells, demanding broad neutralization. This study aimed to develop a virus-like particle (VLP) platform that displays gL\/gH and gB in a dense, repetitive array to overcome these barriers. Methods: We conjugated recombinant gL\/gH and gB to Acinetobacter phage AP205 VLPs using SpyTag\/SpyCatcher covalent linkage, generating monovalent and bivalent chimeric nanoparticles (co-displaying both antigens on the same particle). Mice were immunized with these VLP constructs or alum-adjuvanted soluble proteins, and antibody responses, neutralization titres against B-cell and epithelial-cell infection, as well as germinal centre responses and durability, were assessed over a four-month period. Results: AP205-conjugated nanoparticles elicited significantly higher antigen-specific IgG titres than soluble proteins. The chimeric VLP, co-displaying gL\/gH and gB, induced the stronger neutralising antibodies, effectively blocking EBV entry into both B cells and epithelial cells. Mechanistically, VLP immunization drove robust and sustained germinal centre reactions, resulting in increased plasma and memory B cells, and maintained neutralising activity for at least four months. Conclusions: Precision nanoscale assembly of EBV entry glycoproteins on a synthetic VLP programs high-magnitude, broad-spectrum, and durable humoral immunity. The AP205-SpyTag platform offers a versatile and promising strategy for developing an effective prophylactic EBV vaccine.<\/jats:p>","DOI":"10.3390\/vaccines14090735","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T15:01:07Z","timestamp":1787670067000},"page":"735","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dual Antigen Display on an AP205 VLP Platform Elicits Potent and Durable Neutralization of EBV Infection in B Cells and Epithelial Cells In Vitro"],"prefix":"10.3390","volume":"14","author":[{"given":"Xiaojuan","family":"Han","sequence":"first","affiliation":[{"name":"CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Gao","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Shi","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Li","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China"},{"name":"College of Life Science, University of Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Zhai","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guokai","family":"Feng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Musheng","family":"Zeng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baidong","family":"Hou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Song","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Sciences, Guangxi Academy of Medical Sciences, The People\u2019s Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuping","family":"Zhang","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China"},{"name":"College of Life Science, University of Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,25]]},"reference":[{"key":"ref_1","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":"2016","journal-title":"Nat. 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