tetano
Editor, Senior Moderator
NPJ Vaccines
. 2024 Sep 16;9(1):170.
doi: 10.1038/s41541-024-00963-4. CircRNA based multivalent neuraminidase vaccine induces broad protection against influenza viruses in mice
Xinyu Yue[SUP] #[/SUP][SUP] 1 [/SUP], Cailing Zhong[SUP] #[/SUP][SUP] 2 [/SUP], Rui Cao[SUP] #[/SUP][SUP] 1 [/SUP], Sizhe Liu[SUP] #[/SUP][SUP] 1 [/SUP], Zhiran Qin[SUP] 3 [/SUP], Lin Liu[SUP] 1 [/SUP], Yanmei Zhai[SUP] 1 [/SUP], Wanyu Luo[SUP] 1 [/SUP], Yikai Lian[SUP] 3 [/SUP], Mengjie Zhang[SUP] 3 [/SUP], Hongjie Lu[SUP] 1 [/SUP], Yuanyuan Wang[SUP] 1 [/SUP], Mengxin Xu[SUP] 1 [/SUP], Shuning Liu[SUP] 1 [/SUP], Kexin Lv[SUP] 1 [/SUP], Yuzhu Sun[SUP] 1 [/SUP], Xingchen Zhu[SUP] 1 [/SUP], Haoting Mai[SUP] 1 [/SUP], Jing Liao[SUP] 4 [/SUP], Jingyi Yang[SUP] 5 [/SUP], Lei Deng[SUP] 6 [/SUP], Yang Liu[SUP] 3 [/SUP], Caijun Sun[SUP] 1 [/SUP], Ke-Wei Zheng[SUP] 7 [/SUP], Yuelong Shu[SUP] 8 9 [/SUP], Yao-Qing Chen[SUP] 10 11 12 [/SUP]
Affiliations
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.
. 2024 Sep 16;9(1):170.
doi: 10.1038/s41541-024-00963-4. CircRNA based multivalent neuraminidase vaccine induces broad protection against influenza viruses in mice
Xinyu Yue[SUP] #[/SUP][SUP] 1 [/SUP], Cailing Zhong[SUP] #[/SUP][SUP] 2 [/SUP], Rui Cao[SUP] #[/SUP][SUP] 1 [/SUP], Sizhe Liu[SUP] #[/SUP][SUP] 1 [/SUP], Zhiran Qin[SUP] 3 [/SUP], Lin Liu[SUP] 1 [/SUP], Yanmei Zhai[SUP] 1 [/SUP], Wanyu Luo[SUP] 1 [/SUP], Yikai Lian[SUP] 3 [/SUP], Mengjie Zhang[SUP] 3 [/SUP], Hongjie Lu[SUP] 1 [/SUP], Yuanyuan Wang[SUP] 1 [/SUP], Mengxin Xu[SUP] 1 [/SUP], Shuning Liu[SUP] 1 [/SUP], Kexin Lv[SUP] 1 [/SUP], Yuzhu Sun[SUP] 1 [/SUP], Xingchen Zhu[SUP] 1 [/SUP], Haoting Mai[SUP] 1 [/SUP], Jing Liao[SUP] 4 [/SUP], Jingyi Yang[SUP] 5 [/SUP], Lei Deng[SUP] 6 [/SUP], Yang Liu[SUP] 3 [/SUP], Caijun Sun[SUP] 1 [/SUP], Ke-Wei Zheng[SUP] 7 [/SUP], Yuelong Shu[SUP] 8 9 [/SUP], Yao-Qing Chen[SUP] 10 11 12 [/SUP]
Affiliations
- PMID: 39285168
- DOI: 10.1038/s41541-024-00963-4
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.