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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2024,10,29]]},"abstract":"<jats:p>Antibody responses induced by current vaccines for influenza and SARS-CoV-2 often lack robust cross-reactivity. As hubs where diverse immune cells converge and interact, the alterations in the immune microenvironment within lymph nodes (LNs) are intricately linked to immune responses. Herein, we designed a lipid nanoparticle (LNP) loaded with circular RNA (circRNA) and targeted to LNs, in which CXCL13 was directly integrated into antigen-encoding circRNA strands. We demonstrated that CXCL13 alters the transcriptomic profiles of LNs, especially the upregulation of IL-21 and IL-4. Meanwhile, CXCL13 promotes the formation of germinal center and elicits robust antigen-specific T cell responses. With the codelivery of CXCL13 and the antigen, CXCL13 enhances cross-reactive antibodies against influenza virus and SARS-CoV-2, achieving protection against both homologous and heterologous influenza virus challenges in a mouse model. Notably, the targeted modification of LNP surfaces with antibodies helps address some of the challenges associated with lyophilized LNP vaccines, which is crucial for the long-term storage of LNP-circRNA vaccines. Overall, the circRNA-based antigen-CXCL13 coexpression system developed herein provides a simple and robust platform that enhances the magnitude and breadth of antibody responses against multiple viral glycoproteins, highlighting the potential utility of CXCL13 in inducing broad immune responses.<\/jats:p>","DOI":"10.1073\/pnas.2406434121","type":"journal-article","created":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T11:27:27Z","timestamp":1729596447000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":30,"title":["CXCL13 promotes broad immune responses induced by circular RNA vaccines"],"prefix":"10.1073","volume":"121","author":[{"given":"Jiawu","family":"Wan","sequence":"first","affiliation":[{"name":"National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Hubei Hongshan Laboratory, Wuhan 430070, China"},{"name":"Frontiers Science Center for Animal Breeding 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