{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T07:08:17Z","timestamp":1791443297608,"version":"4.3.3"},"reference-count":45,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,11,12]],"date-time":"2022-11-12T00:00:00Z","timestamp":1668211200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,11,12]],"date-time":"2022-11-12T00:00:00Z","timestamp":1668211200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Coalition for Epidemic Preparedness Innovations (CEPI)"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["npj Vaccines"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Since the first outbreak in December 2019, SARS-CoV-2 has been constantly evolving and five variants have been classified as Variant of Concern (VOC) by the World Health Organization (WHO). These VOCs were found to enhance transmission and\/or decrease neutralization capabilities of monoclonal antibodies and vaccine-induced antibodies. Here, we successfully designed and produced a recombinant COVID-19 vaccine in CHO cells at a high yield. The vaccine antigen contains four hot spot substitutions, K417N, E484K, N501Y and D614G, based on a prefusion-stabilized spike trimer of SARS-CoV-2 (S-6P) and formulated with an Alum\/CpG 7909 dual adjuvant system. Results of immunogenicity studies showed that the variant vaccine elicited robust cross-neutralizing antibody responses against SARS-CoV-2 prototype (Wuhan) strain and all 5 VOCs. It further, stimulated a T<jats:sub>H<\/jats:sub>1 (T Helper type 1) cytokine profile and substantial CD4<jats:sup>+<\/jats:sup> T cell responses in BALB\/c mice and rhesus macaques were recorded. Protective efficacy of the vaccine candidate was evaluated in hamster and rhesus macaque models of SARS-CoV-2. In Golden Syrian hamsters challenged with Beta or Delta strains, the vaccine candidate reduced the viral loads in nasal turbinates and lung tissues, accompanied by significant weight gain and relieved inflammation in the lungs. In rhesus macaque challenged with prototype SARS-CoV-2, the vaccine candidate decreased viral shedding in throat, anal, blood swabs over time, reduced viral loads of bronchus and lung tissue, and effectively relieved the lung pathological inflammatory response. Together, our data demonstrated the broadly neutralizing activity and efficacy of the variant vaccine against both prototype and current VOCs of SARS-CoV-2, justifying further clinical development.<\/jats:p>","DOI":"10.1038\/s41541-022-00571-0","type":"journal-article","created":{"date-parts":[[2022,11,12]],"date-time":"2022-11-12T15:03:18Z","timestamp":1668265398000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["A potent, broadly protective vaccine against SARS-CoV-2 variants of concern"],"prefix":"10.1038","volume":"7","author":[{"given":"Ziyan","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiao","family":"An","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunpeng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pin","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiadai","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianjun","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuanqi","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binbin","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linlin","family":"Bao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujiao","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiayao","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongdong","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanxiang","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Likang","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingyun","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wuxiang","family":"Guan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1918-3578","authenticated-orcid":false,"given":"Chenliang","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongyu","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3234-9616","authenticated-orcid":false,"given":"Zhiming","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangning","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3953-3782","authenticated-orcid":false,"given":"Chao","family":"Shan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ge","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,11,12]]},"reference":[{"key":"571_CR1","unstructured":"WHO. WHO Coronavirus (COVID-19) Dashboard. https:\/\/covid19.who.int\/ (2022)."},{"key":"571_CR2","unstructured":"CDC. Monitoring Variant Proportions. https:\/\/covid.cdc.gov\/covid-data-tracker\/#variant-proportions (2022)."},{"key":"571_CR3","unstructured":"WHO. Classification of Omicron (B.1.1.529): SARS-CoV-2 Variant of Concern. https:\/\/www.who.int\/news\/item\/26-11-2021-classification-of-omicron-(b.1.1.529)-sars-cov-2-variant-of-concern (2021)."},{"key":"571_CR4","unstructured":"WHO. Tracking SARS-CoV-2 variants. https:\/\/www.who.int\/en\/activities\/tracking-SARS-CoV-2-variants (2022)."},{"key":"571_CR5","doi-asserted-by":"publisher","unstructured":"Davies, N. G. et al. Estimated transmissibility and impact of SARS-CoV-2 lineage B.1.1.7 in England. Science https:\/\/doi.org\/10.1126\/science.abg3055 (2021).","DOI":"10.1126\/science.abg3055"},{"key":"571_CR6","doi-asserted-by":"publisher","first-page":"2384","DOI":"10.1016\/j.cell.2021.03.036","volume":"184","author":"M Hoffmann","year":"2021","unstructured":"Hoffmann, M. et al. SARS-CoV-2 variants B.1.351 and P.1 escape from neutralizing antibodies. Cell 184, 2384\u20132393 (2021). e2312.","journal-title":"Cell"},{"key":"571_CR7","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1038\/s41591-021-01285-x","volume":"27","author":"CK Wibmer","year":"2021","unstructured":"Wibmer, C. K. et al. SARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma. Nat. Med 27, 622\u2013625 (2021).","journal-title":"Nat. Med"},{"key":"571_CR8","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1038\/s41586-021-03471-w","volume":"593","author":"S Cele","year":"2021","unstructured":"Cele, S. et al. Escape of SARS-CoV-2 501Y.V2 from neutralization by convalescent plasma. Nature 593, 142\u2013146 (2021).","journal-title":"Nature"},{"key":"571_CR9","doi-asserted-by":"publisher","first-page":"1501","DOI":"10.1126\/science.abd0826","volume":"369","author":"CL Hsieh","year":"2020","unstructured":"Hsieh, C. L. et al. Structure-based design of prefusion-stabilized SARS-CoV-2 spikes. Science 369, 1501\u20131505 (2020).","journal-title":"Science"},{"key":"571_CR10","doi-asserted-by":"publisher","first-page":"7001","DOI":"10.1016\/j.vaccine.2021.10.066","volume":"39","author":"H Liu","year":"2021","unstructured":"Liu, H. et al. Development of recombinant COVID-19 vaccine based on CHO-produced, prefusion spike trimer and alum\/CpG adjuvants. Vaccine 39, 7001\u20137011 (2021).","journal-title":"Vaccine"},{"key":"571_CR11","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1038\/s41586-020-2196-x","volume":"581","author":"R Wolfel","year":"2020","unstructured":"Wolfel, R. et al. Virological assessment of hospitalized patients with COVID-2019. Nature 581, 465\u2013469 (2020).","journal-title":"Nature"},{"key":"571_CR12","doi-asserted-by":"publisher","unstructured":"Dagotto, G. et al. Comparison of subgenomic and total RNA in SARS-CoV-2 challenged Rhesus Macaques. J. Virol. https:\/\/doi.org\/10.1128\/JVI.02370-20 (2021).","DOI":"10.1128\/JVI.02370-20"},{"key":"571_CR13","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1038\/s41577-020-0323-4","volume":"20","author":"PJ Hotez","year":"2020","unstructured":"Hotez, P. J., Corry, D. B. & Bottazzi, M. E. COVID-19 vaccine design: the Janus face of immune enhancement. Nat. Rev. Immunol. 20, 347\u2013348 (2020).","journal-title":"Nat. Rev. Immunol."},{"key":"571_CR14","doi-asserted-by":"crossref","unstructured":"Hadj Hassine, I. Covid-19 vaccines and variants of concern: a review. Rev. Med Virol. 32, e2313, (2021).","DOI":"10.1002\/rmv.2313"},{"key":"571_CR15","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1038\/s41586-020-2895-3","volume":"592","author":"JA Plante","year":"2021","unstructured":"Plante, J. A. et al. Spike mutation D614G alters SARS-CoV-2 fitness. Nature 592, 116\u2013121 (2021).","journal-title":"Nature"},{"key":"571_CR16","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.chom.2020.11.012","volume":"29","author":"D Weissman","year":"2021","unstructured":"Weissman, D. et al. D614G spike mutation increases SARS CoV-2 susceptibility to neutralization. Cell Host Microbe 29, 23\u201331 (2021). e24.","journal-title":"Cell Host Microbe"},{"key":"571_CR17","doi-asserted-by":"publisher","DOI":"10.1038\/s41541-021-00411-7","volume":"6","author":"M Brinkkemper","year":"2021","unstructured":"Brinkkemper, M. et al. A third SARS-CoV-2 spike vaccination improves neutralization of variants-of-concern. NPJ Vaccines 6, 146 (2021).","journal-title":"NPJ Vaccines"},{"key":"571_CR18","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1080\/07853890.2022.2031274","volume":"54","author":"Q Fernandes","year":"2022","unstructured":"Fernandes, Q. et al. Emerging COVID-19 variants and their impact on SARS-CoV-2 diagnosis, therapeutics and vaccines. Ann. Med 54, 524\u2013540 (2022).","journal-title":"Ann. Med"},{"key":"571_CR19","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28528-w","volume":"13","author":"Y Wang","year":"2022","unstructured":"Wang, Y. et al. Structural basis for SARS-CoV-2 Delta variant recognition of ACE2 receptor and broadly neutralizing antibodies. Nat. Commun. 13, 871 (2022).","journal-title":"Nat. Commun."},{"key":"571_CR20","doi-asserted-by":"publisher","unstructured":"Chen, L. L. et al. Impact of SARS-CoV-2 variant-associated RBD mutations on the susceptibility to serum antibodies elicited by COVID-19 infection or vaccination. Clin. Infect. Dis. https:\/\/doi.org\/10.1093\/cid\/ciab656 (2021).","DOI":"10.1093\/cid\/ciab656"},{"key":"571_CR21","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1016\/j.chom.2021.01.014","volume":"29","author":"Z Liu","year":"2021","unstructured":"Liu, Z. et al. Identification of SARS-CoV-2 spike mutations that attenuate monoclonal and serum antibody neutralization. Cell Host Microbe 29, 477\u2013488 (2021). e474.","journal-title":"Cell Host Microbe"},{"key":"571_CR22","doi-asserted-by":"publisher","unstructured":"Lu, L. et al. Neutralization of SARS-CoV-2 Omicron variant by sera from BNT162b2 or Coronavac vaccine recipients. Clin. Infect. Dis. https:\/\/doi.org\/10.1093\/cid\/ciab1041 (2021).","DOI":"10.1093\/cid\/ciab1041"},{"key":"571_CR23","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1126\/science.abf6840","volume":"371","author":"AA Cohen","year":"2021","unstructured":"Cohen, A. A. et al. Mosaic nanoparticles elicit cross-reactive immune responses to zoonotic coronaviruses in mice. Science 371, 735\u2013741 (2021).","journal-title":"Science"},{"key":"571_CR24","doi-asserted-by":"publisher","first-page":"5432","DOI":"10.1016\/j.cell.2021.09.015","volume":"184","author":"AC Walls","year":"2021","unstructured":"Walls, A. C. et al. Elicitation of broadly protective sarbecovirus immunity by receptor-binding domain nanoparticle vaccines. Cell 184, 5432\u20135447 (2021). e5416.","journal-title":"Cell"},{"key":"571_CR25","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1126\/science.abi4506","volume":"373","author":"DR Martinez","year":"2021","unstructured":"Martinez, D. R. et al. Chimeric spike mRNA vaccines protect against Sarbecovirus challenge in mice. Science 373, 991\u2013998 (2021).","journal-title":"Science"},{"key":"571_CR26","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1016\/j.immuni.2019.08.007","volume":"51","author":"TJ Ruckwardt","year":"2019","unstructured":"Ruckwardt, T. J., Morabito, K. M. & Graham, B. S. Immunological lessons from respiratory syncytial virus vaccine development. Immunity 51, 429\u2013442 (2019).","journal-title":"Immunity"},{"key":"571_CR27","doi-asserted-by":"publisher","first-page":"1260","DOI":"10.1126\/science.abb2507","volume":"367","author":"D Wrapp","year":"2020","unstructured":"Wrapp, D. et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science 367, 1260\u20131263 (2020).","journal-title":"Science"},{"key":"571_CR28","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21634-1","volume":"12","author":"JG Liang","year":"2021","unstructured":"Liang, J. G. et al. S-Trimer, a COVID-19 subunit vaccine candidate, induces protective immunity in nonhuman primates. Nat. Commun. 12, 1346 (2021).","journal-title":"Nat. Commun."},{"key":"571_CR29","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1021\/acscentsci.0c00272","volume":"6","author":"C Liu","year":"2020","unstructured":"Liu, C. et al. Research and development on therapeutic agents and vaccines for COVID-19 and related human coronavirus diseases. ACS Cent. Sci. 6, 315\u2013331 (2020).","journal-title":"ACS Cent. Sci."},{"key":"571_CR30","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-88283-8","volume":"11","author":"CE Lien","year":"2021","unstructured":"Lien, C. E. et al. CpG-adjuvanted stable prefusion SARS-CoV-2 spike protein protected hamsters from SARS-CoV-2 challenge. Sci. Rep. 11, 8761 (2021).","journal-title":"Sci. Rep."},{"key":"571_CR31","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-77077-z","volume":"10","author":"TY Kuo","year":"2020","unstructured":"Kuo, T. Y. et al. Development of CpG-adjuvanted stable prefusion SARS-CoV-2 spike antigen as a subunit vaccine against COVID-19. Sci. Rep. 10, 20085 (2020).","journal-title":"Sci. Rep."},{"key":"571_CR32","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1038\/s41421-021-00350-6","volume":"7","author":"S Sun","year":"2021","unstructured":"Sun, S. et al. Broad neutralization against SARS-CoV-2 variants induced by a next-generation protein vaccine V-01. Cell Disco. 7, 114 (2021).","journal-title":"Cell Disco."},{"key":"571_CR33","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1038\/nri2510","volume":"9","author":"P Marrack","year":"2009","unstructured":"Marrack, P., McKee, A. S. & Munks, M. W. Towards an understanding of the adjuvant action of aluminium. Nat. Rev. Immunol. 9, 287\u2013293 (2009).","journal-title":"Nat. Rev. Immunol."},{"key":"571_CR34","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.1016\/S1473-3099(21)00127-4","volume":"21","author":"S Yang","year":"2021","unstructured":"Yang, S. et al. Safety and immunogenicity of a recombinant tandem-repeat dimeric RBD-based protein subunit vaccine (ZF2001) against COVID-19 in adults: two randomised, double-blind, placebo-controlled, phase 1 and 2 trials. Lancet Infect. Dis. 21, 1107\u20131119 (2021).","journal-title":"Lancet Infect. Dis."},{"key":"571_CR35","doi-asserted-by":"publisher","first-page":"1055","DOI":"10.1128\/CVI.00131-10","volume":"17","author":"SA Plotkin","year":"2010","unstructured":"Plotkin, S. A. Correlates of protection induced by vaccination. Clin. Vaccin. Immunol. 17, 1055\u20131065 (2010).","journal-title":"Clin. Vaccin. Immunol."},{"key":"571_CR36","doi-asserted-by":"publisher","unstructured":"Haynes, B. F. et al. Prospects for a safe COVID-19 vaccine. Sci. Transl. Med. https:\/\/doi.org\/10.1126\/scitranslmed.abe0948 (2020).","DOI":"10.1126\/scitranslmed.abe0948"},{"key":"571_CR37","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1038\/nrd2059","volume":"5","author":"AM Krieg","year":"2006","unstructured":"Krieg, A. M. Therapeutic potential of Toll-like receptor 9 activation. Nat. Rev. Drug Disco. 5, 471\u2013484 (2006).","journal-title":"Nat. Rev. Drug Disco."},{"key":"571_CR38","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1007\/s00011-020-01377-3","volume":"69","author":"VV Oberemok","year":"2020","unstructured":"Oberemok, V. V. et al. SARS-CoV-2 will constantly sweep its tracks: a vaccine containing CpG motifs in \u2018lasso\u2019 for the multi-faced virus. Inflamm. Res 69, 801\u2013812 (2020).","journal-title":"Inflamm. Res"},{"key":"571_CR39","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1016\/j.cell.2021.12.033","volume":"185","author":"WF Garcia-Beltran","year":"2022","unstructured":"Garcia-Beltran, W. F. et al. mRNA-based COVID-19 vaccine boosters induce neutralizing immunity against SARS-CoV-2 Omicron variant. Cell 185, 457\u2013466 (2022). e454.","journal-title":"Cell"},{"key":"571_CR40","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1016\/j.cmi.2021.10.005","volume":"28","author":"T Fiolet","year":"2022","unstructured":"Fiolet, T., Kherabi, Y., MacDonald, C. J., Ghosn, J. & Peiffer-Smadja, N. Comparing COVID-19 vaccines for their characteristics, efficacy and effectiveness against SARS-CoV-2 and variants of concern: a narrative review. Clin. Microbiol Infect. 28, 202\u2013221 (2022).","journal-title":"Clin. Microbiol Infect."},{"key":"571_CR41","doi-asserted-by":"publisher","unstructured":"Shen, X. et al. SARS-CoV-2 variant B.1.1.7 is susceptible to neutralizing antibodies elicited by ancestral Spike vaccines. bioRxiv https:\/\/doi.org\/10.1101\/2021.01.27.428516 (2021).","DOI":"10.1101\/2021.01.27.428516"},{"key":"571_CR42","doi-asserted-by":"publisher","first-page":"2352","DOI":"10.1056\/NEJMc2103740","volume":"384","author":"X Shen","year":"2021","unstructured":"Shen, X. et al. Neutralization of SARS-CoV-2 Variants B.1.429 and B.1.351. N. Engl. J. Med 384, 2352\u20132354 (2021).","journal-title":"N. Engl. J. Med"},{"key":"571_CR43","doi-asserted-by":"publisher","unstructured":"Hu, J. et al. Reduced neutralization of SARS-CoV-2 B.1.617 variant by convalescent and vaccinated sera. Genes Dis. https:\/\/doi.org\/10.1016\/j.gendis.2021.11.007 (2021).","DOI":"10.1016\/j.gendis.2021.11.007"},{"key":"571_CR44","unstructured":"ClinicalTrials.gov. Safety and immunogenicity study of a SARS\u2010CoV\u20102 (COVID\u201019) variant vaccine (mRNA\u20101273.351) in na\u00efve and previously vaccinated adults. Rev. Med. Virol. https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04785144 (2022)."},{"key":"571_CR45","doi-asserted-by":"publisher","DOI":"10.1038\/s41541-021-00414-4","volume":"6","author":"JM Carmen","year":"2021","unstructured":"Carmen, J. M. et al. SARS-CoV-2 ferritin nanoparticle vaccine induces robust innate immune activity driving polyfunctional spike-specific T cell responses. NPJ Vaccines 6, 151 (2021).","journal-title":"NPJ Vaccines"}],"container-title":["npj Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41541-022-00571-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41541-022-00571-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41541-022-00571-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,12]],"date-time":"2022-11-12T15:09:22Z","timestamp":1668265762000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41541-022-00571-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,12]]},"references-count":45,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["571"],"URL":"https:\/\/doi.org\/10.1038\/s41541-022-00571-0","relation":{},"ISSN":["2059-0105"],"issn-type":[{"value":"2059-0105","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,12]]},"assertion":[{"value":"4 March 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 October 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 November 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Z.W., C.Z., J.A., J.L., Q.Z., C.H., C.Z., Y.S., X.C., D.H., Y.J., L.S., L.Z., J.F. and G.L. are employees of Shanghai Zerun Biotech Co., Ltd., Shanghai, China. The other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"144"}}