{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:20:15Z","timestamp":1790727615674,"version":"4.1.0"},"reference-count":51,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,4,27]],"date-time":"2024-04-27T00:00:00Z","timestamp":1714176000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,4,27]],"date-time":"2024-04-27T00:00:00Z","timestamp":1714176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["92169104"],"award-info":[{"award-number":["92169104"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82341041"],"award-info":[{"award-number":["82341041"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sig Transduct Target Ther"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Developing a mucosal vaccine against SARS-CoV-2 is critical for combatting the epidemic. Here, we investigated long-term immune responses and protection against SARS-CoV-2 for the intranasal vaccination of a triple receptor-binding domain (RBD) scaffold protein (3R-NC) adjuvanted with a flagellin protein (KFD) (<jats:italic>3R-NC<\/jats:italic>\u2009+\u2009<jats:italic>KFDi.n<\/jats:italic>). In mice, the vaccination elicited RBD-specific broad-neutralizing antibody responses in both serum and mucosal sites sustained at high level over a year. This long-lasting humoral immunity was correlated with the presence of long-lived RBD-specific IgG- and IgA-producing plasma cells, alongside the Th17 and Tfh17-biased T-cell responses driven by the KFD adjuvant. Based upon these preclinical findings, an open labeled clinical trial was conducted in individuals who had been primed with the inactivated SARS-CoV-2 (IAV) vaccine. With a favorable safety profile, the <jats:italic>3R-NC<\/jats:italic>\u2009+\u2009<jats:italic>KFDi.n<\/jats:italic> boost elicited enduring broad-neutralizing IgG in plasma and IgA in salivary secretions. To meet the challenge of frequently emerged variants, we further designed an updated triple-RBD scaffold protein with mutated RBD combinations, which can induce adaptable antibody responses to neutralize the newly emerging variants, including JN.1. Our findings highlight the potential of the KFD-adjuvanted triple-RBD scaffold protein is a promising prototype for the development of a mucosal vaccine against SARS-CoV-2 infection.<\/jats:p>","DOI":"10.1038\/s41392-024-01822-3","type":"journal-article","created":{"date-parts":[[2024,4,27]],"date-time":"2024-04-27T09:01:51Z","timestamp":1714208511000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Nasal vaccination of triple-RBD scaffold protein with flagellin elicits long-term protection against SARS-CoV-2 variants including JN.1"],"prefix":"10.1038","volume":"9","author":[{"given":"Xian","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengxin","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shasha","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei-Qin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixiang","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuning","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunqi","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haofeng","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bowen","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingguo","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8089-163X","authenticated-orcid":false,"given":"Zheng-Li","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0384-8598","authenticated-orcid":false,"given":"Ke","family":"Lan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1300-4652","authenticated-orcid":false,"given":"Yu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7243-8429","authenticated-orcid":false,"given":"Huimin","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4659-1550","authenticated-orcid":false,"given":"Yao-Qing","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,4,27]]},"reference":[{"key":"1822_CR1","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1038\/s41586-021-04387-1","volume":"602","author":"S Cele","year":"2022","unstructured":"Cele, S. et al. Omicron extensively but incompletely escapes Pfizer BNT162b2 neutralization. Nature 602, 654\u2013656 (2022).","journal-title":"Nature"},{"key":"1822_CR2","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1038\/s41421-022-00501-3","volume":"8","author":"J Wang","year":"2022","unstructured":"Wang, J. et al. SARS-CoV-2 vaccination-infection pattern imprints and diversifies T cell differentiation and neutralizing response against Omicron subvariants. Cell Discov. 8, 136 (2022).","journal-title":"Cell Discov."},{"key":"1822_CR3","doi-asserted-by":"crossref","unstructured":"Qu, P. et al. Immune evasion, infectivity, and fusogenicity of SARS-CoV-2 BA.2.86 and FLip variants. Cell 187, 585\u2013595 e586 (2024).","DOI":"10.1016\/j.cell.2023.12.026"},{"key":"1822_CR4","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1016\/j.chom.2022.11.016","volume":"31","author":"DM Morens","year":"2023","unstructured":"Morens, D. M., Taubenberger, J. K. & Fauci, A. S. Rethinking next-generation vaccines for coronaviruses, influenzaviruses, and other respiratory viruses. Cell Host Microbe 31, 146\u2013157 (2023).","journal-title":"Cell Host Microbe"},{"key":"1822_CR5","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1038\/s41586-022-04399-5","volume":"602","author":"JM Carre\u00f1o","year":"2022","unstructured":"Carre\u00f1o, J. M. et al. Activity of convalescent and vaccine serum against SARS-CoV-2 Omicron. Nature 602, 682\u2013688 (2022).","journal-title":"Nature"},{"key":"1822_CR6","doi-asserted-by":"publisher","first-page":"896","DOI":"10.1016\/j.cell.2022.02.005","volume":"185","author":"S Afkhami","year":"2022","unstructured":"Afkhami, S. et al. Respiratory mucosal delivery of next-generation COVID-19 vaccine provides robust protection against both ancestral and variant strains of SARS-CoV-2. Cell 185, 896\u2013915.e19 (2022).","journal-title":"Cell"},{"key":"1822_CR7","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abo3332","volume":"15","author":"Y Zhao","year":"2023","unstructured":"Zhao, Y. et al. Vaccination with S(pan), an antigen guided by SARS-CoV-2 S protein evolution, protects against challenge with viral variants in mice. Sci. Transl. Med. 15, eabo3332 (2023).","journal-title":"Sci. Transl. Med."},{"key":"1822_CR8","doi-asserted-by":"publisher","first-page":"1142","DOI":"10.1056\/NEJMc2216233","volume":"388","author":"D Li","year":"2023","unstructured":"Li, D. et al. Neutralization of BQ.1, BQ.1.1, and XBB with RBD-dimer vaccines. N. Engl. J. Med. 388, 1142\u20131145 (2023).","journal-title":"N. Engl. J. Med."},{"key":"1822_CR9","doi-asserted-by":"publisher","first-page":"e148517","DOI":"10.1172\/JCI148517","volume":"131","author":"JH Ahn","year":"2021","unstructured":"Ahn, J. H. et al. Nasal ciliated cells are primary targets for SARS-CoV-2 replication in the early stage of COVID-19. J. Clin. Invest. 131, e148517 (2021).","journal-title":"J. Clin. Invest."},{"key":"1822_CR10","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1016\/S2213-2600(22)00087-X","volume":"10","author":"JX Li","year":"2022","unstructured":"Li, J. X. et al. Safety and immunogenicity of heterologous boost immunisation with an orally administered aerosolised Ad5-nCoV after two-dose priming with an inactivated SARS-CoV-2 vaccine in Chinese adults: a randomised, open-label, single-centre trial. Lancet Respir. Med. 10, 739\u2013748 (2022).","journal-title":"Lancet Respir. Med."},{"key":"1822_CR11","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1016\/S2213-2600(22)00131-X","volume":"10","author":"F Zhu","year":"2022","unstructured":"Zhu, F. et al. Safety and immunogenicity of a live-attenuated influenza virus vector-based intranasal SARS-CoV-2 vaccine in adults: randomised, double-blind, placebo-controlled, phase 1 and 2 trials. Lancet Respir. Med. 10, 749\u2013760 (2022).","journal-title":"Lancet Respir. Med."},{"key":"1822_CR12","doi-asserted-by":"publisher","first-page":"1903","DOI":"10.1056\/NEJMoa066092","volume":"357","author":"IJ Amanna","year":"2007","unstructured":"Amanna, I. J., Carlson, N. E. & Slifka, M. K. Duration of humoral immunity to common viral and vaccine antigens. N. Engl. J. Med. 357, 1903\u20131915 (2007).","journal-title":"N. Engl. J. Med."},{"key":"1822_CR13","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1038\/s41577-021-00550-x","volume":"21","author":"D Cromer","year":"2021","unstructured":"Cromer, D. et al. Prospects for durable immune control of SARS-CoV-2 and prevention of reinfection. Nat. Rev. Immunol. 21, 395\u2013404 (2021).","journal-title":"Nat. Rev. Immunol."},{"key":"1822_CR14","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1080\/22221751.2022.2031311","volume":"11","author":"C Ma","year":"2022","unstructured":"Ma, C. et al. Drastic decline in sera neutralization against SARS-CoV-2 Omicron variant in Wuhan COVID-19 convalescents. Emerg. microbes Infect. 11, 567\u2013572 (2022).","journal-title":"Emerg. microbes Infect."},{"key":"1822_CR15","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1038\/s41423-021-00643-6","volume":"18","author":"W Wang","year":"2021","unstructured":"Wang, W., Huang, B., Zhu, Y., Tan, W. & Zhu, M. Ferritin nanoparticle-based SARS-CoV-2 RBD vaccine induces a persistent antibody response and long-term memory in mice. Cell Mol. Immunol. 18, 749\u2013751 (2021).","journal-title":"Cell Mol. Immunol."},{"key":"1822_CR16","doi-asserted-by":"publisher","first-page":"2138","DOI":"10.3389\/fimmu.2019.02138","volume":"10","author":"DC Nguyen","year":"2019","unstructured":"Nguyen, D. C., Joyner, C. J., Sanz, I. & Lee, F. E. Factors affecting early antibody secreting cell maturation into long-lived plasma cells. Front. Immunol. 10, 2138 (2019).","journal-title":"Front. Immunol."},{"key":"1822_CR17","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1016\/j.cell.2019.03.016","volume":"177","author":"JG Cyster","year":"2019","unstructured":"Cyster, J. G. & Allen, C. D. C. B cell responses: cell interaction dynamics and decisions. Cell 177, 524\u2013540 (2019).","journal-title":"Cell"},{"key":"1822_CR18","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1111\/imr.13013","volume":"303","author":"DC Nguyen","year":"2021","unstructured":"Nguyen, D. C. et al. Plasma cell survival: the intrinsic drivers, migratory signals, and extrinsic regulators. Immunol. Rev. 303, 138\u2013153 (2021).","journal-title":"Immunol. Rev."},{"key":"1822_CR19","doi-asserted-by":"publisher","first-page":"1564","DOI":"10.1038\/s41590-022-01345-5","volume":"23","author":"X Liu","year":"2022","unstructured":"Liu, X., Yao, J., Zhao, Y., Wang, J. & Qi, H. Heterogeneous plasma cells and long-lived subsets in response to immunization, autoantigen and microbiota. Nat. Immunol. 23, 1564\u20131576 (2022).","journal-title":"Nat. Immunol."},{"key":"1822_CR20","doi-asserted-by":"publisher","first-page":"1279","DOI":"10.1056\/NEJMoa2208343","volume":"387","author":"S Chalkias","year":"2022","unstructured":"Chalkias, S. et al. A bivalent Omicron-containing booster vaccine against Covid-19. N. Engl. J. Med. 387, 1279\u20131291 (2022).","journal-title":"N. Engl. J. Med."},{"key":"1822_CR21","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1038\/s41590-021-01088-9","volume":"23","author":"RC Brewer","year":"2022","unstructured":"Brewer, R. C. et al. BNT162b2 vaccine induces divergent B cell responses to SARS-CoV-2 S1 and S2. Nat. Immunol. 23, 33\u201339 (2022).","journal-title":"Nat. Immunol."},{"key":"1822_CR22","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1038\/s41422-022-00631-z","volume":"32","author":"Z Liu","year":"2022","unstructured":"Liu, Z. et al. A pan-sarbecovirus vaccine induces highly potent and durable neutralizing antibody responses in non-human primates against SARS-CoV-2 Omicron variant. Cell Res. 32, 495\u2013497 (2022).","journal-title":"Cell Res."},{"key":"1822_CR23","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109401","volume":"36","author":"B Zhao","year":"2021","unstructured":"Zhao, B. et al. A safe and effective mucosal RSV vaccine in mice consisting of RSV phosphoprotein and flagellin variant. Cell Rep. 36, 109401 (2021).","journal-title":"Cell Rep."},{"key":"1822_CR24","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1093\/jleuko\/qiad030","volume":"113","author":"X Li","year":"2023","unstructured":"Li, X. et al. Enhanced TLR5-dependent migration and activation of antigen-loaded airway dendritic cells by flagellin. J. Leukoc. Biol. 113, 567\u2013576 (2023).","journal-title":"J. Leukoc. Biol."},{"key":"1822_CR25","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-10247-8","volume":"7","author":"J Yang","year":"2017","unstructured":"Yang, J. et al. Second-generation Flagellin-rPAc fusion protein, KFD2-rPAc, shows high protective efficacy against dental caries with low potential side effects. Sci. Rep. 7, 11191 (2017).","journal-title":"Sci. Rep."},{"key":"1822_CR26","doi-asserted-by":"publisher","first-page":"1279","DOI":"10.1038\/s41423-022-00929-3","volume":"19","author":"J Yang","year":"2022","unstructured":"Yang, J. et al. A triple-RBD-based mucosal vaccine provides broad protection against SARS-CoV-2 variants of concern. Cell Mol. Immunol. 19, 1279\u20131289 (2022).","journal-title":"Cell Mol. Immunol."},{"key":"1822_CR27","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1038\/s41392-021-00610-7","volume":"6","author":"B He","year":"2021","unstructured":"He, B. et al. Rapid isolation and immune profiling of SARS-CoV-2 specific memory B cell in convalescent COVID-19 patients via LIBRA-seq. Signal Transduct. Target Ther. 6, 195 (2021).","journal-title":"Signal Transduct. Target Ther."},{"key":"1822_CR28","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1038\/s41392-023-01421-8","volume":"8","author":"J Yang","year":"2023","unstructured":"Yang, J. et al. The protective nasal boosting of a triple-RBD subunit vaccine against SARS-CoV-2 following inactivated virus vaccination. Signal Transduct. Target Ther. 8, 151 (2023).","journal-title":"Signal Transduct. Target Ther."},{"key":"1822_CR29","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1189\/jlb.3HI0816-368RR","volume":"102","author":"Y Cao","year":"2017","unstructured":"Cao, Y. et al. Frontline science: nasal epithelial GM-CSF contributes to TLR5-mediated modulation of airway dendritic cells and subsequent IgA response. J. Leukoc. Biol. 102, 575\u2013587 (2017).","journal-title":"J. Leukoc. Biol."},{"key":"1822_CR30","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1038\/s41392-021-00704-2","volume":"6","author":"Z Niu","year":"2021","unstructured":"Niu, Z. et al. N501Y mutation imparts cross-species transmission of SARS-CoV-2 to mice by enhancing receptor binding. Signal Transduct. Target Ther. 6, 284 (2021).","journal-title":"Signal Transduct. Target Ther."},{"key":"1822_CR31","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2021.103643","volume":"73","author":"H Shuai","year":"2021","unstructured":"Shuai, H. et al. Emerging SARS-CoV-2 variants expand species tropism to murines. EBioMedicine 73, 103643 (2021).","journal-title":"EBioMedicine"},{"key":"1822_CR32","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1038\/s41586-022-04441-6","volume":"603","author":"PJ Halfmann","year":"2022","unstructured":"Halfmann, P. J. et al. SARS-CoV-2 Omicron virus causes attenuated disease in mice and hamsters. Nature 603, 687\u2013692 (2022).","journal-title":"Nature"},{"key":"1822_CR33","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1038\/s41586-022-04856-1","volume":"607","author":"R Uraki","year":"2022","unstructured":"Uraki, R. et al. Characterization and antiviral susceptibility of SARS-CoV-2 Omicron BA.2. Nature 607, 119\u2013127 (2022).","journal-title":"Nature"},{"key":"1822_CR34","doi-asserted-by":"publisher","first-page":"1603","DOI":"10.1126\/science.abc4730","volume":"369","author":"H Gu","year":"2020","unstructured":"Gu, H. et al. Adaptation of SARS-CoV-2 in BALB\/c mice for testing vaccine efficacy. Science 369, 1603\u20131607 (2020).","journal-title":"Science"},{"key":"1822_CR35","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-34633-7","volume":"13","author":"J Wang","year":"2022","unstructured":"Wang, J. et al. A fourth dose of the inactivated SARS-CoV-2 vaccine redistributes humoral immunity to the N-terminal domain. Nat. Commun. 13, 6866 (2022).","journal-title":"Nat. Commun."},{"key":"1822_CR36","first-page":"521","volume":"614","author":"Y Cao","year":"2023","unstructured":"Cao, Y. et al. Imprinted SARS-CoV-2 humoral immunity induces convergent Omicron RBD evolution. Nature 614, 521\u2013529 (2023).","journal-title":"Nature"},{"key":"1822_CR37","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1016\/j.jconrel.2021.01.012","volume":"331","author":"S Zinkhan","year":"2021","unstructured":"Zinkhan, S. et al. The impact of size on particle drainage dynamics and antibody response. J. Control Release 331, 296\u2013308 (2021).","journal-title":"J. Control Release"},{"key":"1822_CR38","doi-asserted-by":"publisher","first-page":"2425","DOI":"10.1016\/j.immuni.2023.08.011","volume":"56","author":"S Ols","year":"2023","unstructured":"Ols, S. et al. Multivalent antigen display on nanoparticle immunogens increases B cell clonotype diversity and neutralization breadth to pneumoviruses. Immunity 56, 2425\u20132441.e14 (2023).","journal-title":"Immunity"},{"key":"1822_CR39","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1038\/s41577-019-0244-2","volume":"20","author":"M Akkaya","year":"2020","unstructured":"Akkaya, M., Kwak, K. & Pierce, S. K. B cell memory: building two walls of protection against pathogens. Nat. Rev. Immunol. 20, 229\u2013238 (2020).","journal-title":"Nat. Rev. Immunol."},{"key":"1822_CR40","doi-asserted-by":"publisher","first-page":"956","DOI":"10.3389\/fimmu.2019.00956","volume":"10","author":"MK Slifka","year":"2019","unstructured":"Slifka, M. K. & Amanna, I. J. Role of multivalency and antigenic threshold in generating protective antibody responses. Front. Immunol. 10, 956 (2019).","journal-title":"Front. Immunol."},{"key":"1822_CR41","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1038\/mi.2015.38","volume":"9","author":"A Lemke","year":"2016","unstructured":"Lemke, A. et al. Long-lived plasma cells are generated in mucosal immune responses and contribute to the bone marrow plasma cell pool in mice. Mucosal Immunol. 9, 83\u201397 (2016).","journal-title":"Mucosal Immunol."},{"key":"1822_CR42","doi-asserted-by":"publisher","first-page":"1132","DOI":"10.1016\/j.immuni.2019.04.011","volume":"50","author":"S Crotty","year":"2019","unstructured":"Crotty, S. T follicular helper cell biology: a decade of discovery and diseases. Immunity 50, 1132\u20131148 (2019).","journal-title":"Immunity"},{"key":"1822_CR43","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1084\/jem.20091706","volume":"207","author":"DT Avery","year":"2010","unstructured":"Avery, D. T. et al. B cell-intrinsic signaling through IL-21 receptor and STAT3 is required for establishing long-lived antibody responses in humans. J. Exp. Med. 207, 155\u2013171 (2010).","journal-title":"J. Exp. Med."},{"key":"1822_CR44","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1016\/j.immuni.2014.10.004","volume":"41","author":"S Crotty","year":"2014","unstructured":"Crotty, S. T follicular helper cell differentiation, function, and roles in disease. Immunity 41, 529\u2013542 (2014).","journal-title":"Immunity"},{"key":"1822_CR45","doi-asserted-by":"publisher","first-page":"4213","DOI":"10.4049\/jimmunol.169.8.4213","volume":"169","author":"HA Minges Wols","year":"2002","unstructured":"Minges Wols, H. A., Underhill, G. H., Kansas, G. S. & Witte, P. L. The role of bone marrow-derived stromal cells in the maintenance of plasma cell longevity. J. Immunol. 169, 4213\u20134221 (2002).","journal-title":"J. Immunol."},{"key":"1822_CR46","doi-asserted-by":"publisher","first-page":"1084","DOI":"10.4161\/hv.23809","volume":"9","author":"J Yang","year":"2013","unstructured":"Yang, J. et al. Antigen replacement of domains D2 and D3 in flagellin promotes mucosal IgA production and attenuates flagellin-induced inflammatory response after intranasal immunization. Hum. Vaccin. Immunother. 9, 1084\u20131092 (2013).","journal-title":"Hum. Vaccin. Immunother."},{"key":"1822_CR47","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1189\/jlb.1VMR0216-096RR","volume":"100","author":"E Ferretti","year":"2016","unstructured":"Ferretti, E., Ponzoni, M., Doglioni, C. & Pistoia, V. IL-17 superfamily cytokines modulate normal germinal center B cell migration. J. Leukoc. Biol. 100, 913\u2013918 (2016).","journal-title":"J. Leukoc. Biol."},{"key":"1822_CR48","doi-asserted-by":"publisher","first-page":"1739","DOI":"10.1038\/s41423-020-00540-4","volume":"18","author":"K Ma","year":"2021","unstructured":"Ma, K. et al. IL-17 sustains the plasma cell response via p38-mediated Bcl-xL RNA stability in lupus pathogenesis. Cell Mol. Immunol. 18, 1739\u20131750 (2021).","journal-title":"Cell Mol. Immunol."},{"key":"1822_CR49","doi-asserted-by":"publisher","first-page":"e157332","DOI":"10.1172\/jci.insight.157332","volume":"7","author":"V Kim","year":"2022","unstructured":"Kim, V. et al. IL-17-producing follicular Th cells enhance plasma cell differentiation in lupus-prone mice. JCI Insight 7, e157332 (2022).","journal-title":"JCI Insight"},{"key":"1822_CR50","doi-asserted-by":"publisher","first-page":"666","DOI":"10.1038\/s41584-020-00519-5","volume":"16","author":"J Clarke","year":"2020","unstructured":"Clarke, J. IL-17 sustains plasma cells in SLE. Nat. Rev. Rheumatol. 16, 666 (2020).","journal-title":"Nat. Rev. Rheumatol."},{"key":"1822_CR51","doi-asserted-by":"publisher","first-page":"e82217","DOI":"10.7554\/eLife.82217","volume":"12","author":"X Gao","year":"2023","unstructured":"Gao, X. et al. T follicular helper 17 (Tfh17) cells are superior for immunological memory maintenance. Elife 12, e82217 (2023).","journal-title":"Elife"}],"container-title":["Signal Transduction and Targeted Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41392-024-01822-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41392-024-01822-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41392-024-01822-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,27]],"date-time":"2024-04-27T09:01:56Z","timestamp":1714208516000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41392-024-01822-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,27]]},"references-count":51,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["1822"],"URL":"https:\/\/doi.org\/10.1038\/s41392-024-01822-3","relation":{},"ISSN":["2059-3635"],"issn-type":[{"value":"2059-3635","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,27]]},"assertion":[{"value":"11 December 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 March 2024","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 April 2024","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 April 2024","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Animal studies were conducted according to the Regulations for Administration of Affairs Concerning Experimental Animals in China, and approved by the Animal Welfare and Ethical Review Committee of Wuhan Institute of Virology (WIV), Chinese Academy of Sciences (CAS) (study numbers WIVA09202101). The infection experiments on BALB\/c mice were performed in the Animal Biosafety Level 3 (ABSL-3) Laboratory of Wuhan University, which were approved by the Institutional Animal Care and Use Committee (AUP #WP2022-0044) and the Institutional Biosafety Committee (IBC, Protocol #S0132240E). Human experiment was an open-label, non-controlled pilot study of the investigator-initiated trial, which was reviewed and approved by Shanghai Public Health Clinical Center (approval number 2022-S090-03, registration number ChiCTR2400081625), and conducted from 23 December 2022 to 30 April 2023. Written informed consent was obtained from all SARS-CoV-2 uninfected volunteers. All adverse events were identified according to the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). Any adverse events from the beginning of each dose to 7 days post treatment were taken as the adverse events.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}],"article-number":"114"}}