CircRNA based multivalent neuraminidase vaccine induces broad protection against influenza viruses in mice

Autor: Xinyu Yue, Cailing Zhong, Rui Cao, Sizhe Liu, Zhiran Qin, Lin Liu, Yanmei Zhai, Wanyu Luo, Yikai Lian, Mengjie Zhang, Hongjie Lu, Yuanyuan Wang, Mengxin Xu, Shuning Liu, Kexin Lv, Yuzhu Sun, Xingchen Zhu, Haoting Mai, Jing Liao, Jingyi Yang, Lei Deng, Yang Liu, Caijun Sun, Ke-Wei Zheng, Yuelong Shu, Yao-Qing Chen
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: npj Vaccines, Vol 9, Iss 1, Pp 1-13 (2024)
Druh dokumentu: article
ISSN: 2059-0105
DOI: 10.1038/s41541-024-00963-4
Popis: Abstract Developing broad-spectrum influenza vaccines is crucial for influenza control and potential pandemic preparedness. Here, we reported a novel vaccine design utilizing circular RNA (circRNA) as a delivery platform for multi-subtype neuraminidases (NA) (influenza A N1, N2, and influenza B Victoria lineage NA) immunogens. Individual NA circRNA lipid nanoparticles (LNP) elicited robust NA-specific antibody responses with neuraminidase inhibition activity (NAI), preventing the virus from egressing and infecting neighboring cells. Additionally, the administration of circRNA LNP induced cellular immunity in mice. To achieve a universal influenza vaccine, we combined all three subtypes of NA circRNA-LNPs to generate a trivalent circRNA vaccine. The trivalent vaccine elicited a balanced antibody response against all three NA subtypes and a Th1-biased immune response in mice. Moreover, it protected mice against the lethal challenge of matched and mismatched H1N1, H3N2, and influenza B viruses, encompassing circulating and ancestral influenza virus strains. This study highlights the potential of delivering multiple NA antigens through circRNA-LNPs as a promising strategy for effectively developing a universal influenza vaccine against diverse influenza viruses.
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