| Download | - View accepted manuscript: Lipid nanoparticle encapsulation improves effectiveness of a Delta Spike-CD40L DNA vaccine against homologous and heterologous SARS-CoV-2 challenge in Syrian hamsters (PDF, 27.2 MiB)
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| DOI | Resolve DOI: https://doi.org/10.1016/j.omtm.2024.101325 |
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| Author | Search for: Tamming, LeviORCID identifier: https://orcid.org/0000-0003-2851-7311; Search for: Duque, Diana; Search for: Tran, Anh1ORCID identifier: https://orcid.org/0000-0003-0644-6014; Search for: Lansdell, Casey; Search for: Frahm, Grant; Search for: Wu, Jianguo; Search for: Fekete, Emily E. F.; Search for: Creskey, Marybeth; Search for: Raman, Sathya; Search for: Laryea, Emmanuel; Search for: Zhang, Wanyue; Search for: Pfeifle, Annabelle; Search for: Gravel, Caroline; Search for: Stalker, Andrew; Search for: Hashem, Anwar M.; Search for: Chen, Wangxue1ORCID identifier: https://orcid.org/0000-0003-0958-7728; Search for: Stuible, Matthew1ORCID identifier: https://orcid.org/0009-0002-4403-0677; Search for: Durocher, Yves1ORCID identifier: https://orcid.org/0000-0002-2268-4111; Search for: Safronetz, David; Search for: Cao, Jingxin; Search for: Wang, Lisheng; Search for: Sauve, Simon; Search for: Rosu-Myles, Michael; Search for: Zhang, Xu; Search for: Johnston, Michael J. W.; Search for: Li, Xuguang |
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| Affiliation | - National Research Council of Canada. Human Health Therapeutics
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| Funder | Search for: Health Canada; Search for: National Research Council Canada |
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| Format | Text, Article |
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| Subject | SARS-CoV-2; lipid nanoparticle; DNA vaccine; nucleic acid; antibody |
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| Abstract | The effectiveness of mRNA vaccines largely depends on their lipid nanoparticle (LNP) component. Herein, we investigate the effectiveness of DLin-KC2-DMA (KC2) and SM-102-based LNPs for the intramuscular delivery of a plasmid encoding B.1.617.2 (Delta) Spike fused with CD40 ligand. LNP-encapsulation of this CD40L-adjuvanted DNA vaccine with either LNP formulation drastically enhanced antibody responses, enabling neutralization of heterologous Omicron variants. The DNA-LNP formulations provided excellent protection from homologous challenge, reducing viral replication, and preventing histopathological changes in the pulmonary tissues. Moreover, the DNA-LNP vaccines maintained a high level of protection against heterologous Omicron BA.5 challenge despite a reduced neutralizing response. In addition, we observed that DNA-LNP vaccination led to the pulmonary downregulation of interferon signaling, IL-12 signaling and macrophage response pathways following SARS-CoV-2 challenge, shedding some light on the mechanisms underlying the prevention of pulmonary injury. These results highlight the potential combination of molecular adjuvants with LNP-based vaccine delivery to induce greater and broader immune responses capable of preventing inflammatory damage and protecting against emerging variants. These findings could be informative for the future design of both DNA and mRNA vaccines. |
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| Publication date | 2024-08-19 |
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| Publisher | Elsevier |
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| Licence | |
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| In | |
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| Language | English |
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| In press | Yes |
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| Peer reviewed | Yes |
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| Identifier | S2329050124001414 |
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| Export citation | Export as RIS |
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| Report a correction | Report a correction (opens in a new tab) |
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| Record identifier | 50b9cee6-a527-490d-a74b-61f34eb0efe6 |
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| Record created | 2024-09-10 |
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| Record modified | 2024-09-10 |
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