{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T13:32:32Z","timestamp":1782135152064,"version":"3.54.5"},"reference-count":32,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,7,20]],"date-time":"2024-07-20T00:00:00Z","timestamp":1721433600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Program of China","award":["2022YFC2304302"],"award-info":[{"award-number":["2022YFC2304302"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Respiratory syncytial virus (RSV) is a serious human respiratory pathogen that commonly affects children, older adults, and immunocompromised individuals. At present, the design of licensed vaccines focuses on the incorporation of the pre-fusion protein (PreF protein) of RSV, as this protein has the ability to induce antibodies that offer a high level of protection. Moreover, the G protein contains the CX3C motif that binds the chemokine receptor CX3CR1 in respiratory epithelial cells, which plays an essential role in viral infection. Therefore, incorporating the G antigen into vaccine design may prove more advantageous for RSV prevention. In this study, we developed a human adenoviral vector-based RSV vaccine containing highly neutralizing immunogens, a modified full-length PreF protein fused with the central conserved peptides of the G protein (Gcc) from both RSV subgroups trimerized via a C-terminal foldon, and evaluated its immune response in mice through intranasal (i.n.) immunization. Our results showed that immunization with Ad5-PreF-Qa-Gcc elicited a balanced Th1\/Th2 immune response and robust mucosal immunity with higher neutralizing antibody titers against RSV Long and RSV B1. Importantly, immunization with Ad5-PreF-Qa-Gcc enhanced CD4+ CD25+ FoxP3+ Treg cell response and protected the mice against RSV infection. Our data demonstrate that the combination of Gcc and the PreF antigen is a viable strategy for developing effective RSV vaccines.<\/jats:p>","DOI":"10.3390\/vaccines12070807","type":"journal-article","created":{"date-parts":[[2024,7,23]],"date-time":"2024-07-23T11:40:36Z","timestamp":1721734836000},"page":"807","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The Central Conserved Peptides of Respiratory Syncytial Virus G Protein Enhance the Immune Response to the RSV F Protein in an Adenovirus Vector Vaccine Candidate"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-1995-6021","authenticated-orcid":false,"given":"Pengdi","family":"Chai","sequence":"first","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases (NITFID), NHC Key Laboratory for Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Shi","sequence":"additional","affiliation":[{"name":"College of Public Health, Gansu University of Chinese Medicine, Lanzhou 730101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjie","family":"Yu","sequence":"additional","affiliation":[{"name":"College of Public Health, Gansu University of Chinese Medicine, Lanzhou 730101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiafei","family":"Liu","sequence":"additional","affiliation":[{"name":"The First Clinical Medical Institute, Henan University of Chinese Medicine, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongwei","family":"Li","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases (NITFID), NHC Key Laboratory for Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinsong","family":"Li","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases (NITFID), NHC Key Laboratory for Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Li","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases (NITFID), NHC Key Laboratory for Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandi","family":"Li","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases (NITFID), NHC Key Laboratory for Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaojun","family":"Duan","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases (NITFID), NHC Key Laboratory for Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"10-1128","DOI":"10.1128\/mSphere.00237-21","article-title":"Human Respiratory Syncytial Virus Subgroup A and B Infections in Nasal, Bronchial, Small-Airway, and Organoid-Derived Respiratory Cultures","volume":"6","author":"Rijsbergen","year":"2021","journal-title":"mSphere"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e2022215","DOI":"10.1590\/1984-0462\/2024\/42\/2022215","article-title":"Evaluation of Severe Acute Respiratory Syndrome surveillance caused by respiratory viruses in a pediatric unit, 2013 to 2019","volume":"42","author":"Freitas","year":"2023","journal-title":"Rev. Paul. Pediatr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"10-1128","DOI":"10.1128\/JCM.01828-20","article-title":"Global Molecular Epidemiology of Respiratory Syncytial Virus from the 2017\u20132018 INFORM-RSV Study","volume":"59","author":"Tabor","year":"2020","journal-title":"J. Clin. Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Fuentes, S., Coyle, E.M., Beeler, J., Golding, H., and Khurana, S. (2016). Antigenic Fingerprinting following Primary RSV Infection in Young Children Identifies Novel Antigenic Sites and Reveals Unlinked Evolution of Human Antibody Repertoires to Fusion and Attachment Glycoproteins. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1005554"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"8193","DOI":"10.1128\/JVI.00133-15","article-title":"Nonglycosylated G-Protein Vaccine Protects against Homologous and Heterologous Respiratory Syncytial Virus (RSV) Challenge, while Glycosylated G Enhances RSV Lung Pathology and Cytokine Levels","volume":"89","author":"Fuentes","year":"2015","journal-title":"J. Virol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/s41579-019-0149-x","article-title":"Respiratory syncytial virus entry and how to block it","volume":"17","author":"Battles","year":"2019","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1705","DOI":"10.1099\/0022-1317-68-6-1705","article-title":"Appearance of a soluble form of the G protein of respiratory syncytial virus in fluids of infected cells","volume":"68","author":"Hendricks","year":"1987","journal-title":"J. Gen. Virol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2543","DOI":"10.1099\/vir.0.000218","article-title":"CX3CR1 is an important surface molecule for respiratory syncytial virus infection in human airway epithelial cells","volume":"96","author":"Chirkova","year":"2015","journal-title":"J. Gen. Virol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Johnson, S.M., McNally, B.A., Ioannidis, I., Flano, E., Teng, M.N., Oomens, A.G., Walsh, E.E., and Peeples, M.E. (2015). Respiratory Syncytial Virus Uses CX3CR1 as a Receptor on Primary Human Airway Epithelial Cultures. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1005318"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1016\/j.ymthe.2023.02.012","article-title":"Protein expression\/secretion boost by a novel unique 21-mer cis-regulatory motif (Exin21) via mRNA stabilization","volume":"31","author":"Zhu","year":"2023","journal-title":"Mol. Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.virol.2022.08.017","article-title":"Codon-optimization of the respiratory syncytial virus (RSV) G protein expressed in a vesicular stomatitis virus (VSV) vector improves immune responses in a cotton rat model","volume":"575","author":"Brakel","year":"2022","journal-title":"Virology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"8143","DOI":"10.1038\/ncomms9143","article-title":"A highly stable prefusion RSV F vaccine derived from structural analysis of the fusion mechanism","volume":"6","author":"Krarup","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1038\/s41541-022-00487-9","article-title":"Immunogenicity and protective efficacy of RSV G central conserved domain vaccine with a prefusion nanoparticle","volume":"7","author":"Pavot","year":"2022","journal-title":"NPJ Vaccines"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1038\/s41421-021-00360-4","article-title":"Heterologous prime-boost immunizations with chimpanzee adenoviral vectors elicit potent and protective immunity against SARS-CoV-2 infection","volume":"7","author":"Liu","year":"2021","journal-title":"Cell Discov."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1128\/jcm.26.8.1595-1597.1988","article-title":"Formalin-inactivated respiratory syncytial virus vaccine induces antibodies to the fusion glycoprotein that are deficient in fusion-inhibiting activity","volume":"26","author":"Murphy","year":"1988","journal-title":"J. Clin. Microbiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"6656","DOI":"10.1016\/j.vaccine.2019.09.041","article-title":"Antigenicity and immunogenicity of unique prefusion-mimic F proteins presented on enveloped virus-like particles","volume":"37","author":"Kwon","year":"2019","journal-title":"Vaccine"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Luo, J., Qin, H., Lei, L., Lou, W., Li, R., and Pan, Z. (2022). Virus-like particles containing a prefusion-stabilized F protein induce a balanced immune response and confer protection against respiratory syncytial virus infection in mice. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1054005"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2092","DOI":"10.1056\/NEJMoa2104840","article-title":"Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination","volume":"384","author":"Greinacher","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"102681","DOI":"10.1016\/j.jaut.2021.102681","article-title":"Comparison of vaccine-induced thrombotic events between ChAdOx1 nCoV-19 and Ad26.COV.2.S vaccines","volume":"122","author":"Hwang","year":"2021","journal-title":"J. Autoimmun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/j.cell.2022.02.005","article-title":"Respiratory mucosal delivery of next-generation COVID-19 vaccine provides robust protection against both ancestral and variant strains of SARS-CoV-2","volume":"185","author":"Afkhami","year":"2022","journal-title":"Cell"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1099\/vir.0.81660-0","article-title":"Protection of mice against Human respiratory syncytial virus by wild-type and aglycosyl mouse-human chimaeric IgG antibodies to subgroup-conserved epitopes on the G glycoprotein","volume":"87","author":"Mekseepralard","year":"2006","journal-title":"J. Gen. Virol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1056\/NEJMoa2213836","article-title":"Efficacy and Safety of a Bivalent RSV Prefusion F Vaccine in Older Adults","volume":"388","author":"Walsh","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1056\/NEJMoa2207566","article-title":"Efficacy and Safety of an Ad26.RSV.preF-RSV preF Protein Vaccine in Older Adults","volume":"388","author":"Falsey","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.antiviral.2014.07.016","article-title":"Co-immunization with virus-like particle and DNA vaccines induces protection against respiratory syncytial virus infection and bronchiolitis","volume":"110","author":"Hwang","year":"2014","journal-title":"Antiviral Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/s41541-020-0200-y","article-title":"Adenovector 26 encoded prefusion conformation stabilized RSV-F protein induces long-lasting Th1-biased immunity in neonatal mice","volume":"5","author":"Bolder","year":"2020","journal-title":"NPJ Vaccines"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4265","DOI":"10.1016\/j.vaccine.2018.05.112","article-title":"Orally administered adenoviral-based vaccine induces respiratory mucosal memory and protection against RSV infection in cotton rats","volume":"36","author":"Joyce","year":"2018","journal-title":"Vaccine"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3019","DOI":"10.1128\/JVI.00036-09","article-title":"Regulatory T cells promote early influx of CD8+ T cells in the lungs of respiratory syncytial virus-infected mice and diminish immunodominance disparities","volume":"83","author":"Ruckwardt","year":"2009","journal-title":"J. Virol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2382","DOI":"10.4049\/jimmunol.1000423","article-title":"Foxp3+ CD4 regulatory T cells limit pulmonary immunopathology by modulating the CD8 T cell response during respiratory syncytial virus infection","volume":"185","author":"Fulton","year":"2010","journal-title":"J. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2987","DOI":"10.1073\/pnas.1217580110","article-title":"Defective immunoregulation in RSV vaccine-augmented viral lung disease restored by selective chemoattraction of regulatory T cells","volume":"110","author":"Loebbermann","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"10946","DOI":"10.1128\/JVI.01295-13","article-title":"Regulatory T cells prevent Th2 immune responses and pulmonary eosinophilia during respiratory syncytial virus infection in mice","volume":"87","author":"Durant","year":"2013","journal-title":"J. Virol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.biologicals.2009.02.017","article-title":"The cotton rat model of respiratory viral infections","volume":"37","author":"Boukhvalova","year":"2009","journal-title":"Biologicals"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Cox, F., Saeland, E., Thoma, A., van den Hoogen, W., Tettero, L., Drijver, J., Vaneman, C., van Polanen, Y., Ritschel, T., and Bastian, A.R. (2023). RSV A2-Based Prefusion F Vaccine Candidates Induce RSV A and RSV B Cross Binding and Neutralizing Antibodies and Provide Protection against RSV A and RSV B Challenge in Preclinical Models. Vaccines, 11.","DOI":"10.3390\/vaccines11030672"}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/12\/7\/807\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:20:19Z","timestamp":1760109619000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/12\/7\/807"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,20]]},"references-count":32,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,7]]}},"alternative-id":["vaccines12070807"],"URL":"https:\/\/doi.org\/10.3390\/vaccines12070807","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,20]]}}}