CircRNA based multivalent neuraminidase vaccine induces broad protection against influenza viruses in mice
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.
Authors
- Caijun Sun (ORCID: https://orcid.org/0000-0002-2000-7053)
- Xingchen Zhu (ORCID: https://orcid.org/0009-0002-2739-6650)
- Kexin Lv
- Wanyu Luo
- Jing Liao (ORCID: https://orcid.org/0000-0001-6613-2696)
- Mengxin Xu (ORCID: https://orcid.org/0000-0002-3826-7371)
- Haoting Mai
- Lei Deng (ORCID: https://orcid.org/0000-0002-2818-0432)
- Yao-Qing Chen (ORCID: https://orcid.org/0000-0002-4659-1550)
- Hongjie Lu
- Ke‐wei Zheng (ORCID: https://orcid.org/0000-0002-4110-4776)
- Rui Cao (ORCID: https://orcid.org/0000-0001-5873-0733)
- Xinyu Yue
- Cailing Zhong (ORCID: https://orcid.org/0000-0003-3585-6311)
- Yanmei Zhai
- Lin Liu (ORCID: https://orcid.org/0000-0002-7728-0317)
- Sizhe Liu (ORCID: https://orcid.org/0000-0003-1877-5448)
- Shuning Liu (ORCID: https://orcid.org/0000-0003-4473-8237)
- Yuzhu Sun (ORCID: https://orcid.org/0000-0002-4776-592X)
- Yuelong Shu (ORCID: https://orcid.org/0000-0001-9279-0916)
- Jingyi Yang (ORCID: https://orcid.org/0009-0005-4577-3327)
- Yang Liu
- Zhiran Qin
- Yikai Lian
- Yuanyuan Wang
- Mengjie Zhang (ORCID: https://orcid.org/0009-0009-1501-1742)
Institutions
- Sun Yat-sen University (CN)
- Hunan University (CN)
- Shenzhen University (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Shenzhen Bay Laboratory (CN)
- Shanghai Public Health Clinical Center (CN)
- Institute of Laboratory Animal Science (CN)
- Shenzhen University Health Science Center (CN)
- Guangzhou Medical University (CN)
Publication Details
- Journal
- npj Vaccines
- Published
- 2024-09-16
- DOI
- https://doi.org/10.1038/s41541-024-00963-4
- Citations
- 26
- Primary Topic
- Influenza Virus Research Studies
- Type
- article
- Field-Weighted Citation Impact
- 10.05
Funders
- National Natural Science Foundation of China
- Science and Technology Planning Project of Guangdong Province