{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T05:22:48Z","timestamp":1787376168937,"version":"build-2736575974"},"reference-count":46,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100018537","name":"National Science and Technology Major Project","doi-asserted-by":"crossref","award":["2025ZD01900706"],"award-info":[{"award-number":["2025ZD01900706"]}],"id":[{"id":"10.13039\/501100018537","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Yunnan Science and Technology Talent and Platform Program","award":["202605AS350013"],"award-info":[{"award-number":["202605AS350013"]}]},{"name":"Yunnan Science and Technology Talent and Platform Program","award":["202505AK340009"],"award-info":[{"award-number":["202505AK340009"]}]},{"name":"Science and Technology Leading Talent Program of Yunnan Province","award":["202405AB350002"],"award-info":[{"award-number":["202405AB350002"]}]},{"name":"High\u2013Level Medical Talent Training Program of Yunnan Province","award":["L-2024018"],"award-info":[{"award-number":["L-2024018"]}]},{"name":"CAMS Innovation Fund for Medical Sciences","award":["2022-I2M-3-001"],"award-info":[{"award-number":["2022-I2M-3-001"]}]},{"name":"Project of Basic Research in Yunnan Province","award":["202301AT070365"],"award-info":[{"award-number":["202301AT070365"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background\/Objectives: Nipah virus (NiV) is a highly pathogenic zoonotic agent that causes fatal respiratory and neurological diseases, for which no approved vaccines are currently available. To address this unmet need, we developed and evaluated novel mRNA-LNP vaccine candidates. These vaccines employ an epitope- and structure\u2013guided \u201cimmune-focusing\u201d strategy, aiming to maximize the exposure of critical neutralizing epitopes on the viral attachment (G) and fusion (F) glycoproteins. Methods: Head-to-head dimeric antigens (2Gs and 2Fs) were engineered by removing subdominant stalk regions and tandemly duplicating epitope-rich globular head domains. Three LNP-encapsulated candidates-NV1 (encoding 2Gs), NV2 (encoding 2Fs), and NV3 (a 1:1 mixture of NV1 and NV2)-were evaluated in BALB\/c mice and Syrian hamsters to systematically assess humoral responses, cytokine secretion, BCR\/TCR repertoires, and systemic safety. Results: NV1 and NV3 induced potent binding antibodies and strong neutralizing activity against NiV pseudoviruses. Meanwhile, although NV2 lacked neutralizing activity, it induced superior Th1-biased cellular immunity, accompanied by extensive T-cell clonal proliferation. BCR\/TCR sequencing revealed unique adaptive immune characteristics that perfectly align with the distinct immunogenic properties described above. Preliminary safety assessments found no toxicity to vital organs, while active germinal center formation confirmed the success of immune mobilization. Conclusions: An epitope-centered dimer design effectively shapes the unique defense mechanisms of the adaptive immune system. NV3 offers a balanced and synergistic strategy that combines potent humoral and cellular immune defenses, providing a highly promising platform for the development of a Nipah virus (NiV) vaccine.<\/jats:p>","DOI":"10.3390\/vaccines14080718","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T10:55:18Z","timestamp":1787223318000},"page":"718","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Epitope-Based Nipah Virus G and F Head-to-Head Dimer mRNA Vaccines Exhibit Distinct Immunogenicity and Immune Profiles"],"prefix":"10.3390","volume":"14","author":[{"given":"Rui","family":"Peng","sequence":"first","affiliation":[{"name":"Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming 650118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiali","family":"Xu","sequence":"additional","affiliation":[{"name":"Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming 650118, China"},{"name":"Yunnan Key Laboratory of Cross-Border Infectious Disease Control and Prevention and Novel Drug Development, Yunnan University, Kunming 650118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longhai","family":"Yuan","sequence":"additional","affiliation":[{"name":"Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming 650118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bai","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming 650118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9879-2744","authenticated-orcid":false,"given":"Hongyu","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming 650118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Tang","sequence":"additional","affiliation":[{"name":"Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming 650118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming 650118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming 650118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming 650118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6390-9604","authenticated-orcid":false,"given":"Qing","family":"Huang","sequence":"additional","affiliation":[{"name":"Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming 650118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junbin","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming 650118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1675-9735","authenticated-orcid":false,"given":"Shuaiyao","family":"Lu","sequence":"additional","affiliation":[{"name":"Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming 650118, China"},{"name":"State Key Laboratory of Respiratory Health and Multimorbidity, Beijing 100005, China"},{"name":"Key Laboratory of Pathogen Infection Prevention and Control, Ministry of Education, Peking Union Medical College, Beijing 100730, China"},{"name":"Yunnan Provincial Key Laboratory of Vector-Borne Diseases Control and Research, Kunming 650118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,20]]},"reference":[{"key":"ref_1","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":"Singh","year":"2019","journal-title":"Vet. 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