CXCL13 promotes broad immune responses induced by circular RNA vaccines.

Autor:	Wan J; National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China.; Hubei Hongshan Laboratory, Wuhan 430070, China.; Frontiers Science Center for Animal Breeding and Sustainable Production, Wuhan 430070, China.; Key Laboratory of Preventive Veterinary Medicine of Hubei Province, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China., Wang C; National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China.; Hubei Hongshan Laboratory, Wuhan 430070, China.; Frontiers Science Center for Animal Breeding and Sustainable Production, Wuhan 430070, China.; Key Laboratory of Preventive Veterinary Medicine of Hubei Province, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China., Wang Z; National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China.; Hubei Hongshan Laboratory, Wuhan 430070, China.; Frontiers Science Center for Animal Breeding and Sustainable Production, Wuhan 430070, China.; Key Laboratory of Preventive Veterinary Medicine of Hubei Province, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China., Wang L; National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China.; Hubei Hongshan Laboratory, Wuhan 430070, China.; Frontiers Science Center for Animal Breeding and Sustainable Production, Wuhan 430070, China.; Key Laboratory of Preventive Veterinary Medicine of Hubei Province, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China., Wang H; National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China.; Hubei Hongshan Laboratory, Wuhan 430070, China.; Frontiers Science Center for Animal Breeding and Sustainable Production, Wuhan 430070, China.; Key Laboratory of Preventive Veterinary Medicine of Hubei Province, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China., Zhou M; National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China.; Hubei Hongshan Laboratory, Wuhan 430070, China.; Frontiers Science Center for Animal Breeding and Sustainable Production, Wuhan 430070, China.; Key Laboratory of Preventive Veterinary Medicine of Hubei Province, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China., Fu ZF; National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China.; Hubei Hongshan Laboratory, Wuhan 430070, China.; Frontiers Science Center for Animal Breeding and Sustainable Production, Wuhan 430070, China.; Key Laboratory of Preventive Veterinary Medicine of Hubei Province, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China., Zhao L; National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China.; Hubei Hongshan Laboratory, Wuhan 430070, China.; Frontiers Science Center for Animal Breeding and Sustainable Production, Wuhan 430070, China.; Key Laboratory of Preventive Veterinary Medicine of Hubei Province, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2024 Oct 29; Vol. 121 (44), pp. e2406434121. Date of Electronic Publication: 2024 Oct 22.
DOI:	10.1073/pnas.2406434121
Abstrakt:	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. Competing Interests: Competing interests statement:The authors declare no competing interest.
Databáze:	MEDLINE
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