{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T21:44:22Z","timestamp":1787003062399,"version":"build-2736575974"},"reference-count":67,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T00:00:00Z","timestamp":1766361600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T00:00:00Z","timestamp":1766966400000},"content-version":"vor","delay-in-days":7,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100000245","name":"Michael Smith Foundation for Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000245","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"DOI":"10.1038\/s41467-025-66252-3","type":"journal-article","created":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T13:55:02Z","timestamp":1766411702000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A binary self-amplifying expression platform enabling lipid nanoparticle-free vaccines and nanomedicines"],"prefix":"10.1038","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7392-9852","authenticated-orcid":false,"given":"Wilfred A.","family":"Jefferies","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung Bok","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5599-3933","authenticated-orcid":false,"given":"Paolo","family":"Ribeca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suresh","family":"Kari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay A.","family":"Young","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Hui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon Yong","family":"Qi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1381-9157","authenticated-orcid":false,"given":"Emmanuel","family":"Garrovillas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Becky M. Y.","family":"Cho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela","family":"Housh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy","family":"Welch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iryna","family":"Saranchova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryl G.","family":"Pfeifer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,22]]},"reference":[{"key":"66252_CR1","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1056\/NEJMoa2035389","volume":"384","author":"LR Baden","year":"2021","unstructured":"Baden, L. R. et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N. Engl. J. Med. 384, 403\u2013416 (2021).","journal-title":"N. Engl. J. Med"},{"key":"66252_CR2","doi-asserted-by":"publisher","first-page":"2427","DOI":"10.1056\/NEJMoa2028436","volume":"383","author":"EJ Anderson","year":"2020","unstructured":"Anderson, E. J. et al. Safety and immunogenicity of SARS-CoV-2 mRNA-1273 vaccine in older adults. N. Engl. J. Med. 383, 2427\u20132438 (2020).","journal-title":"N. Engl. J. Med."},{"key":"66252_CR3","doi-asserted-by":"publisher","first-page":"2603","DOI":"10.1056\/NEJMoa2034577","volume":"383","author":"FP Polack","year":"2020","unstructured":"Polack, F. P. et al. Safety and efficacy of the BNT162b2 mRNA covid-19 vaccine. N. Engl. J. Med. 383, 2603\u20132615 (2020).","journal-title":"N. Engl. J. Med."},{"key":"66252_CR4","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2021.718753","volume":"9","author":"T Liu","year":"2021","unstructured":"Liu, T., Liang, Y. & Huang, L. Development and delivery systems of mRNA vaccines. Front Bioeng. Biotechnol. 9, 718753 (2021).","journal-title":"Front Bioeng. Biotechnol."},{"key":"66252_CR5","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2021.766764","volume":"9","author":"Y Liang","year":"2021","unstructured":"Liang, Y., Huang, L. & Liu, T. Corrigendum: Development and delivery systems of mRNA vaccines. Front Bioeng. Biotechnol. 9, 766764 (2021).","journal-title":"Front Bioeng. Biotechnol."},{"key":"66252_CR6","doi-asserted-by":"publisher","first-page":"e167","DOI":"10.1002\/mco2.167","volume":"3","author":"Y Gu","year":"2022","unstructured":"Gu, Y., Duan, J., Yang, N., Yang, Y. & Zhao, X. mRNA vaccines in the prevention and treatment of diseases. MedComm 3, e167 (2022).","journal-title":"MedComm"},{"key":"66252_CR7","doi-asserted-by":"publisher","first-page":"1115","DOI":"10.3390\/cimb44030073","volume":"44","author":"M Alden","year":"2022","unstructured":"Alden, M. et al. Intracellular reverse transcription of Pfizer BioNTech COVID-19 mRNA vaccine BNT162b2 in vitro in human liver cell line. Curr. Issues Mol. Biol. 44, 1115\u20131126 (2022).","journal-title":"Curr. Issues Mol. Biol."},{"key":"66252_CR8","doi-asserted-by":"publisher","first-page":"n627","DOI":"10.1136\/bmj.n627","volume":"372","author":"S Tinari","year":"2021","unstructured":"Tinari, S. The EMA covid-19 data leak, and what it tells us about mRNA instability. BMJ 372, n627 (2021).","journal-title":"BMJ"},{"key":"66252_CR9","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1038\/nrd.2017.243","volume":"17","author":"N Pardi","year":"2018","unstructured":"Pardi, N., Hogan, M. J., Porter, F. W. & Weissman, D. mRNA vaccines - a new era in vaccinology. Nat. Rev. Drug Discov. 17, 261\u2013279 (2018).","journal-title":"Nat. Rev. Drug Discov."},{"key":"66252_CR10","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1336906","volume":"15","author":"BZ Igyarto","year":"2024","unstructured":"Igyarto, B. Z. & Qin, Z. The mRNA-LNP vaccines - the good, the bad and the ugly? Front. Immunol. 15, 1336906 (2024).","journal-title":"Front. Immunol."},{"key":"66252_CR11","doi-asserted-by":"crossref","unstructured":"Wang, J. et al. Recent advances in lipid nanoparticles and their safety concerns for mRNA delivery. Vaccines (Basel). 12, 1148 (2024).","DOI":"10.3390\/vaccines12101148"},{"key":"66252_CR12","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1016\/j.stem.2013.06.001","volume":"13","author":"N Yoshioka","year":"2013","unstructured":"Yoshioka, N. et al. Efficient generation of human iPSCs by a synthetic self-replicative RNA. Cell Stem Cell 13, 246\u2013254 (2013).","journal-title":"Cell Stem Cell"},{"key":"66252_CR13","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/bs.adgen.2014.10.005","volume":"89","author":"LA Brito","year":"2015","unstructured":"Brito, L. A. et al. Self-amplifying mRNA vaccines. Adv. Genet 89, 179\u2013233 (2015).","journal-title":"Adv. Genet"},{"key":"66252_CR14","doi-asserted-by":"crossref","unstructured":"Schmidt, C., Schnierle, B. S. Self-amplifying RNA vaccine candidates: alternative platforms for mRNA vaccine development. Pathogens. 12, 138 (2023).","DOI":"10.3390\/pathogens12010138"},{"key":"66252_CR15","doi-asserted-by":"crossref","unstructured":"Blakney, A. K., Ip, S., Geall, A. J. An update on self-amplifying mRNA vaccine development. Vaccines 9, 97 (2021).","DOI":"10.3390\/vaccines9020097"},{"key":"66252_CR16","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1038\/s41573-024-00977-6","volume":"23","author":"PR Cullis","year":"2024","unstructured":"Cullis, P. R. & Felgner, P. L. The 60\u2009year evolution of lipid nanoparticles for nucleic acid delivery. Nat. Rev. Drug Discov. 23, 709\u2013722 (2024).","journal-title":"Nat. Rev. Drug Discov."},{"key":"66252_CR17","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.addr.2020.06.002","volume":"154-155","author":"E Samaridou","year":"2020","unstructured":"Samaridou, E., Heyes, J. & Lutwyche, P. Lipid nanoparticles for nucleic acid delivery: Current perspectives. Adv. Drug Deliv. Rev. 154-155, 37\u201363 (2020).","journal-title":"Adv. Drug Deliv. Rev."},{"key":"66252_CR18","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1038\/s41565-021-00898-0","volume":"16","author":"JA Kulkarni","year":"2021","unstructured":"Kulkarni, J. A. et al. The current landscape of nucleic acid therapeutics. Nat. Nanotechnol. 16, 630\u2013643 (2021).","journal-title":"Nat. Nanotechnol."},{"key":"66252_CR19","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-67797-x","volume":"14","author":"C Davidopoulou","year":"2024","unstructured":"Davidopoulou, C., Kouvelas, D. & Ouranidis, A. COMPARING vaccine manufacturing technologies recombinant DNA vs in vitro transcribed (IVT) mRNA. Sci. Rep. 14, 21742 (2024).","journal-title":"Sci. Rep."},{"key":"66252_CR20","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-52685-1","volume":"14","author":"GB Schober","year":"2024","unstructured":"Schober, G. B., Story, S. & Arya, D. P. A careful look at lipid nanoparticle characterization: analysis of benchmark formulations for encapsulation of RNA cargo size gradient. Sci. Rep. 14, 2403 (2024).","journal-title":"Sci. Rep."},{"key":"66252_CR21","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-33157-4","volume":"13","author":"S Li","year":"2022","unstructured":"Li, S. et al. Payload distribution and capacity of mRNA lipid nanoparticles. Nat. Commun. 13, 5561 (2022).","journal-title":"Nat. Commun."},{"key":"66252_CR22","doi-asserted-by":"publisher","first-page":"1078","DOI":"10.1038\/s41578-021-00358-0","volume":"6","author":"X Hou","year":"2021","unstructured":"Hou, X., Zaks, T., Langer, R. & Dong, Y. Lipid nanoparticles for mRNA delivery. Nat. Rev. Mater. 6, 1078\u20131094 (2021).","journal-title":"Nat. Rev. Mater."},{"key":"66252_CR23","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1038\/s41434-019-0095-2","volume":"26","author":"AK Blakney","year":"2019","unstructured":"Blakney, A. K., McKay, P. F., Yus, B. I., Aldon, Y. & Shattock, R. J. Inside out: optimization of lipid nanoparticle formulations for exterior complexation and in vivo delivery of saRNA. Gene Ther. 26, 363\u2013372 (2019).","journal-title":"Gene Ther."},{"key":"66252_CR24","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.omtn.2019.01.013","volume":"15","author":"KJ Hassett","year":"2019","unstructured":"Hassett, K. J. et al. Optimization of Lipid Nanoparticles for Intramuscular Administration of mRNA Vaccines. Mol. Ther. Nucleic Acids 15, 1\u201311 (2019).","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"66252_CR25","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2309472120","volume":"120","author":"J Chen","year":"2023","unstructured":"Chen, J. et al. Combinatorial design of ionizable lipid nanoparticles for muscle-selective mRNA delivery with minimized off-target effects. Proc. Natl. Acad. Sci. USA 120, e2309472120 (2023).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"66252_CR26","doi-asserted-by":"publisher","first-page":"7509","DOI":"10.7150\/thno.77259","volume":"12","author":"HN Jung","year":"2022","unstructured":"Jung, H. N., Lee, S. Y., Lee, S., Youn, H. & Im, H. J. Lipid nanoparticles for delivery of RNA therapeutics: Current status and the role of in vivo imaging. Theranostics 12, 7509\u20137531 (2022).","journal-title":"Theranostics"},{"key":"66252_CR27","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2303567120","volume":"120","author":"SJ Shepherd","year":"2023","unstructured":"Shepherd, S. J. et al. Throughput-scalable manufacturing of SARS-CoV-2 mRNA lipid nanoparticle vaccines. Proc. Natl. Acad. Sci. USA 120, e2303567120 (2023).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"66252_CR28","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2021.120586","volume":"601","author":"L Schoenmaker","year":"2021","unstructured":"Schoenmaker, L. et al. mRNA-lipid nanoparticle COVID-19 vaccines: Structure and stability. Int. J. Pharm. 601, 120586 (2021).","journal-title":"Int. J. Pharm."},{"key":"66252_CR29","doi-asserted-by":"publisher","first-page":"1571","DOI":"10.1084\/jem.20171450","volume":"215","author":"N Pardi","year":"2018","unstructured":"Pardi, N. et al. Nucleoside-modified mRNA vaccines induce potent T follicular helper and germinal center B cell responses. J. Exp. Med. 215, 1571\u20131588 (2018).","journal-title":"J. Exp. Med."},{"key":"66252_CR30","doi-asserted-by":"crossref","unstructured":"Zhou, W. et al. Vaccines\u2019 new era-RNA vaccine. Viruses. 15, 1760 (2023).","DOI":"10.3390\/v15081760"},{"key":"66252_CR31","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1016\/j.ymthe.2004.07.013","volume":"10","author":"N Tatsis","year":"2004","unstructured":"Tatsis, N. & Ertl, H. C. Adenoviruses as vaccine vectors. Mol. Ther. 10, 616\u2013629 (2004).","journal-title":"Mol. Ther."},{"key":"66252_CR32","doi-asserted-by":"crossref","unstructured":"Moss B., Earl P. L. Overview of the vaccinia virus expression system. Curr. Protoc. Mol. Biol. 16, Unit16 (2002).","DOI":"10.1002\/0471142727.mb1615s60"},{"key":"66252_CR33","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1007\/978-1-4939-1363-3_19","volume":"1205","author":"SK Villwock","year":"2014","unstructured":"Villwock, S. K. & Aparicio, O. M. Two-dimensional agarose gel electrophoresis for analysis of DNA replication. Methods Mol. Biol. 1205, 329\u2013340 (2014).","journal-title":"Methods Mol. Biol."},{"key":"66252_CR34","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1038\/sj.gt.3302213","volume":"11","author":"Z Wang","year":"2004","unstructured":"Wang, Z. et al. Detection of integration of plasmid DNA into host genomic DNA following intramuscular injection and electroporation. Gene Ther. 11, 711\u2013721 (2004).","journal-title":"Gene Ther."},{"key":"66252_CR35","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1007\/978-1-0716-0323-9_5","volume":"2119","author":"KA Mettrick","year":"2020","unstructured":"Mettrick, K. A., Weaver, G. M. & Grainge, I. Neutral-neutral 2-dimensional agarose gel electrophoresis for visualization of E. coli DNA replication structures. Methods Mol. Biol. 2119, 61\u201372 (2020).","journal-title":"Methods Mol. Biol."},{"key":"66252_CR36","doi-asserted-by":"publisher","first-page":"4915","DOI":"10.1128\/MCB.16.9.4915","volume":"16","author":"RF Kalejta","year":"1996","unstructured":"Kalejta, R. F. & Hamlin, J. L. Composite patterns in neutral\/neutral two-dimensional gels demonstrate inefficient replication origin usage. Mol. Cell Biol. 16, 4915\u20134922 (1996).","journal-title":"Mol. Cell Biol."},{"key":"66252_CR37","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1111\/j.1749-6632.1995.tb44729.x","volume":"772","author":"WW Nichols","year":"1995","unstructured":"Nichols, W. W., Ledwith, B. J., Manam, S. V. & Troilo, P. J. Potential DNA vaccine integration into host cell genome. Ann. N. Y Acad. Sci. 772, 30\u201339 (1995).","journal-title":"Ann. N. Y Acad. Sci."},{"key":"66252_CR38","doi-asserted-by":"publisher","first-page":"9987","DOI":"10.1128\/JVI.00751-10","volume":"84","author":"SL Stephen","year":"2010","unstructured":"Stephen, S. L. et al. Chromosomal integration of adenoviral vector DNA in vivo. J. Virol. 84, 9987\u20139994 (2010).","journal-title":"J. Virol."},{"key":"66252_CR39","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15183","volume":"8","author":"B Milholland","year":"2017","unstructured":"Milholland, B. et al. Differences between germline and somatic mutation rates in humans and mice. Nat. Commun. 8, 15183 (2017).","journal-title":"Nat. Commun."},{"key":"66252_CR40","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-12023-w","volume":"10","author":"SJ Lindsay","year":"2019","unstructured":"Lindsay, S. J., Rahbari, R., Kaplanis, J., Keane, T. & Hurles, M. E. Similarities and differences in patterns of germline mutation between mice and humans. Nat. Commun. 10, 4053 (2019).","journal-title":"Nat. Commun."},{"key":"66252_CR41","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-37795-0","volume":"14","author":"E Prompetchara","year":"2023","unstructured":"Prompetchara, E. et al. Immunogenicity and protective efficacy of SARS-CoV-2 mRNA vaccine encoding secreted non-stabilized spike in female mice. Nat. Commun. 14, 2309 (2023).","journal-title":"Nat. Commun."},{"key":"66252_CR42","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-26479-2","volume":"12","author":"J Wei","year":"2021","unstructured":"Wei, J. et al. Anti-spike antibody response to natural SARS-CoV-2 infection in the general population. Nat. Commun. 12, 6250 (2021).","journal-title":"Nat. Commun."},{"key":"66252_CR43","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1016\/j.jconrel.2024.12.003","volume":"378","author":"G Lin","year":"2025","unstructured":"Lin, G. et al. Enhancing protective immunity against SARS-CoV-2 with a self-amplifying RNA lipid nanoparticle vaccine. J. Control Release 378, 250\u2013265 (2025).","journal-title":"J. Control Release"},{"key":"66252_CR44","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-38457-x","volume":"14","author":"M Komori","year":"2023","unstructured":"Komori, M. et al. saRNA vaccine expressing membrane-anchored RBD elicits broad and durable immunity against SARS-CoV-2 variants of concern. Nat. Commun. 14, 2810 (2023).","journal-title":"Nat. Commun."},{"key":"66252_CR45","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/1157023","volume":"2021","author":"AS Sameer","year":"2021","unstructured":"Sameer, A. S. & Nissar, S. Toll-like receptors (TLRs): Structure, functions, signaling, and role of their polymorphisms in colorectal cancer susceptibility. Biomed. Res. Int. 2021, 1157023 (2021).","journal-title":"Biomed. Res. Int."},{"key":"66252_CR46","doi-asserted-by":"publisher","first-page":"1313","DOI":"10.1016\/S0140-6736(22)00151-9","volume":"399","author":"A Khobragade","year":"2022","unstructured":"Khobragade, A. et al. Efficacy, safety, and immunogenicity of the DNA SARS-CoV-2 vaccine (ZyCoV-D): the interim efficacy results of a phase 3, randomised, double-blind, placebo-controlled study in India. Lancet 399, 1313\u20131321 (2022).","journal-title":"Lancet"},{"key":"66252_CR47","doi-asserted-by":"publisher","first-page":"e67137","DOI":"10.1371\/journal.pone.0067137","volume":"8","author":"JA Young","year":"2013","unstructured":"Young, J. A. & Jefferies, W. Towards the conservation of endangered avian species: a recombinant west nile virus vaccine results in increased humoral and cellular immune responses in Japanese quail (Coturnix japonica). PLoS ONE 8, e67137 (2013).","journal-title":"PLoS ONE"},{"key":"66252_CR48","doi-asserted-by":"publisher","first-page":"e36","DOI":"10.1371\/journal.ppat.0010036","volume":"1","author":"TZ Vitalis","year":"2005","unstructured":"Vitalis, T. Z. et al. Using the TAP component of the antigen-processing machinery as a molecular adjuvant. PLoS Pathog. 1, e36 (2005).","journal-title":"PLoS Pathog."},{"key":"66252_CR49","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2025.127748","volume":"64","author":"G Hamonic","year":"2025","unstructured":"Hamonic, G. et al. Safety and immunogenicity of COVAC-2, a Sepivac SWE adjuvanted SARS-CoV-2 recombinant protein vaccine in healthy adults; a randomized controlled first-in-human dose-escalation trial. Vaccine 64, 127748 (2025).","journal-title":"Vaccine"},{"key":"66252_CR50","doi-asserted-by":"publisher","DOI":"10.1080\/08916934.2025.2551517","volume":"58","author":"DJ Speicher","year":"2025","unstructured":"Speicher, D. J., Rose, J. & McKernan, K. Quantification of residual plasmid DNA and SV40 promoter-enhancer sequences in Pfizer\/BioNTech and Moderna modRNA COVID-19 vaccines from Ontario, Canada. Autoimmunity 58, 2551517 (2025).","journal-title":"Autoimmunity"},{"key":"66252_CR51","doi-asserted-by":"publisher","first-page":"1833","DOI":"10.1038\/mt.2008.200","volume":"16","author":"K Kariko","year":"2008","unstructured":"Kariko, K. et al. Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability. Mol. Ther. 16, 1833\u20131840 (2008).","journal-title":"Mol. Ther."},{"key":"66252_CR52","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2021.103479","volume":"24","author":"S Ndeupen","year":"2021","unstructured":"Ndeupen, S. et al. The mRNA-LNP platform\u2019s lipid nanoparticle component used in preclinical vaccine studies is highly inflammatory. iScience 24, 103479 (2021).","journal-title":"iScience"},{"key":"66252_CR53","doi-asserted-by":"publisher","first-page":"2109","DOI":"10.1016\/j.ymthe.2022.04.011","volume":"30","author":"SM Moghimi","year":"2022","unstructured":"Moghimi, S. M. & Simberg, D. Pro-inflammatory concerns with lipid nanoparticles. Mol. Ther. 30, 2109\u20132110 (2022).","journal-title":"Mol. Ther."},{"key":"66252_CR54","doi-asserted-by":"publisher","first-page":"16982","DOI":"10.1021\/acsnano.1c04996","volume":"15","author":"R Tenchov","year":"2021","unstructured":"Tenchov, R., Bird, R., Curtze, A. E. & Zhou, Q. Lipid nanoparticles horizontal line from liposomes to mrna vaccine delivery, a landscape of research diversity and advancement. ACS Nano 15, 16982\u201317015 (2021).","journal-title":"ACS Nano"},{"key":"66252_CR55","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvacx.2022.100189","volume":"11","author":"X Saez-Llorens","year":"2022","unstructured":"Saez-Llorens, X. et al. Safety and immunogenicity of mRNA-LNP COVID-19 vaccine CVnCoV in Latin American adults: a phase 2 randomized study. Vaccin. X 11, 100189 (2022).","journal-title":"Vaccin. X"},{"key":"66252_CR56","doi-asserted-by":"publisher","first-page":"100307","DOI":"10.1016\/j.jvacx.2023.100307","volume":"14","author":"X Saez-Llorens","year":"2023","unstructured":"Saez-Llorens, X. et al. Corrigendum to \u201csafety and immunogenicity of mRNA-LNP COVID-19 vaccine CVnCoV in Latin American adults: a phase 2 randomized study\u201d [Vaccine: X 11 100189]. Vaccin. X 14, 100307 (2023).","journal-title":"Vaccin. X"},{"key":"66252_CR57","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1016\/j.medj.2022.03.009","volume":"3","author":"TL Darling","year":"2022","unstructured":"Darling, T. L. et al. mRNA-1273 and Ad26.COV2.S vaccines protect against the B.1.621 variant of SARS-CoV-2. Med. 3, 309\u201324 e6 (2022).","journal-title":"Med"},{"key":"66252_CR58","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abm3302","volume":"14","author":"B Ying","year":"2022","unstructured":"Ying, B. et al. Protective activity of mRNA vaccines against ancestral and variant SARS-CoV-2 strains. Sci. Transl. Med. 14, eabm3302 (2022).","journal-title":"Sci. Transl. Med."},{"key":"66252_CR59","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1038\/s41591-022-02092-8","volume":"29","author":"SM Scheaffer","year":"2023","unstructured":"Scheaffer, S. M. et al. Bivalent SARS-CoV-2 mRNA vaccines increase breadth of neutralization and protect against the BA.5 Omicron variant in mice. Nat. Med 29, 247\u2013257 (2023).","journal-title":"Nat. Med"},{"key":"66252_CR60","doi-asserted-by":"crossref","unstructured":"Tscherne A., et al. Immunogenicity and efficacy of the COVID-19 candidate vector vaccine MVA-SARS-2-S in preclinical vaccination. Proc. Natl. Acad. Sci. USA. 118, e2026207118 (2021).","DOI":"10.1073\/pnas.2026207118"},{"key":"66252_CR61","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":"66252_CR62","doi-asserted-by":"publisher","first-page":"7394","DOI":"10.1016\/j.vaccine.2021.11.001","volume":"39","author":"K Wu","year":"2021","unstructured":"Wu, K. et al. Variant SARS-CoV-2 mRNA vaccines confer broad neutralization as primary or booster series in mice. Vaccine 39, 7394\u20137400 (2021).","journal-title":"Vaccine"},{"key":"66252_CR63","doi-asserted-by":"publisher","first-page":"1525","DOI":"10.1093\/cid\/ciab686","volume":"74","author":"JL Jacobs","year":"2022","unstructured":"Jacobs, J. L. et al. Severe acute respiratory syndrome coronavirus 2 viremia Is associated With coronavirus disease 2019 severity and predicts clinical outcomes. Clin. Infect. Dis. 74, 1525\u20131533 (2022).","journal-title":"Clin. Infect. Dis."},{"key":"66252_CR64","doi-asserted-by":"crossref","unstructured":"Li, Y. et al. SARS-CoV-2 viremia is associated with distinct proteomic pathways and predicts COVID-19 outcomes. J. Clin. Invest. 131, e148635 (2021).","DOI":"10.1172\/JCI148635"},{"key":"66252_CR65","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2021.115595","volume":"102","author":"K Hagman","year":"2022","unstructured":"Hagman, K. et al. Duration of SARS-CoV-2 viremia and its correlation to mortality and inflammatory parameters in patients hospitalized for COVID-19: a cohort study. Diagn. Microbiol Infect. Dis. 102, 115595 (2022).","journal-title":"Diagn. Microbiol Infect. Dis."},{"key":"66252_CR66","doi-asserted-by":"publisher","first-page":"2731","DOI":"10.4049\/jimmunol.172.5.2731","volume":"172","author":"J Mestas","year":"2004","unstructured":"Mestas, J. & Hughes, C. C. Of mice and not men: differences between mouse and human immunology. J. Immunol. 172, 2731\u20132738 (2004).","journal-title":"J. Immunol."},{"key":"66252_CR67","doi-asserted-by":"crossref","unstructured":"Hnasko, R. ELISA: Methods and Protocols 1 edn (Humana New York, 2015).","DOI":"10.1007\/978-1-4939-2742-5_1"}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41467-025-66252-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-025-66252-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-025-66252-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T20:01:45Z","timestamp":1767038505000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41467-025-66252-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,22]]},"references-count":67,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["66252"],"URL":"https:\/\/doi.org\/10.1038\/s41467-025-66252-3","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,22]]},"assertion":[{"value":"3 May 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 October 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 December 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The University of British Columbia is the owner of the intellectual property associated with this study that is licensed to university start-up company, Eyam Health Inc. With the exception of IS, all authors acknowledge financial holdings and professional affiliations\u00a0or advisory positions with the company; and WAJ acknowledges board membership as CSO.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"11561"}}