{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T02:17:22Z","timestamp":1778811442727,"version":"3.51.4"},"reference-count":51,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T00:00:00Z","timestamp":1663632000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["81991491"],"award-info":[{"award-number":["81991491"]}]},{"name":"National Natural Science Foundation of China","award":["82071783"],"award-info":[{"award-number":["82071783"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Background: Despite considerable efforts toward vaccine development in past decades, no effective vaccines against respiratory syncytial virus (RSV) are available. Recently, we showed that an optimized formalin concentration can preserve prefusion protein (pre-F) on RSV-infected cells and protect mice against RSV infection without causing enhanced respiratory disease (ERD). Here, we sought to further stabilize pre-F on RSV virions by optimizing the production of FI-RSV. Methods: Freshly produced RSV virions were treated with formalin under different concentrations to obtained an opti-FI-RSV vaccine with high pre-F level. Immunogenicity and safety of opti-FI-RSV were evaluated in Balb\/c mice and cotton rats. Results: Using 0.0156\u20130.1778% formalin, we successfully preserved pre-F on virions. This opti-FI-RSV exhibited improved immunogenicity and efficacy without causing ERD. Surprisingly, opti-FI-RSV, with a pre-F-dominant immunogen, still caused ERD after immunization with a suboptimal dose or when the neutralizing antibody titers declined. ERD was avoided by coadministering opti-FI-RSV with CpG + MPLA adjuvant, which subsequently induced a Th1-biasing immune response and, more importantly, significantly improved antibody avidity. Conclusions: Our study provides a new method to obtain a novel FI-RSV vaccine with a high pre-F level and may provide a reference for developing other inactivated vaccines. Our findings also emphasize that appropriate adjuvants are critical for nonreplicating vaccines.<\/jats:p>","DOI":"10.3390\/v14102085","type":"journal-article","created":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T00:08:09Z","timestamp":1663718889000},"page":"2085","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["An Optimized FI-RSV Vaccine Effectively Protects Cotton Rats and BALB\/c Mice without Causing Enhanced Respiratory Disease"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8496-0479","authenticated-orcid":false,"given":"Min","family":"Lin","sequence":"first","affiliation":[{"name":"State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen 361002, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7462-8763","authenticated-orcid":false,"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen 361002, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Fan","family":"Yin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen 361002, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun-Yu","family":"Si","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen 361002, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu-Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen 361002, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen 361002, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue","family":"Lin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen 361002, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying-Bin","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen 361002, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen 361002, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0099-4212","authenticated-orcid":false,"given":"Zi-Zheng","family":"Zheng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen 361002, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0179-5266","authenticated-orcid":false,"given":"Ning-Shao","family":"Xia","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen 361002, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1016\/S2214-109X(18)30408-X","article-title":"Global, regional, and national estimates of pneumonia morbidity and mortality in children younger than 5 years between 2000 and 2015: A systematic analysis","volume":"7","author":"McAllister","year":"2019","journal-title":"Lancet. 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