Nanoparticle-based DNA vaccine protects against SARS-CoV-2 variants in female preclinical models.
In: Nature communications, Jg. 15 (2024-01-18), Heft 1, S. 590
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Zugriff:
A safe and effective vaccine with long-term protection against SARS-CoV-2 variants of concern (VOCs) is a global health priority. Here, we develop lipid nanoparticles (LNPs) to provide safe and effective delivery of plasmid DNA (pDNA) and show protection against VOCs in female small animal models. Using a library of LNPs encapsulating unique barcoded DNA (b-DNA), we screen for b-DNA delivery after intramuscular administration. The top-performing LNPs are further tested for their capacity of pDNA uptake in antigen-presenting cells in vitro. The lead LNP is used to encapsulate pDNA encoding the HexaPro version of SARS-CoV-2 spike (LNP-HPS) and immunogenicity and protection is tested in vivo. LNP-HPS elicit a robust protective effect against SARS-CoV-2 Gamma (P.1), correlating with reduced lethality, decreased viral load in the lungs and reduced lung damage. LNP-HPS induce potent humoral and T cell responses against P.1, and generate high levels of neutralizing antibodies against P.1 and Omicron (B.1.1.529). Our findings indicate that the protective efficacy and immunogenicity elicited by LNP-HPS are comparable to those achieved by the approved COVID-19 vaccine from Biontech/Pfizer in animal models. Together, these findings suggest that LNP-HPS hold great promise as a vaccine candidate against VOCs.
(© 2024. The Author(s).)
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Nanoparticle-based DNA vaccine protects against SARS-CoV-2 variants in female preclinical models.
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Autor/in / Beteiligte Person: | Guimaraes, LC ; Costa, PAC ; Scalzo Júnior, SRA ; Ferreira, HAS ; Braga, ACS ; de Oliveira LC ; Figueiredo, MM ; Shepherd, S ; Hamilton, A ; Queiroz-Junior, CM ; da Silva WN ; da Silva NJA ; Rodrigues Alves, MT ; Santos, AK ; de Faria KKS ; Marim, FM ; Fukumasu, H ; Birbrair, A ; Teixeira-Carvalho, A ; de Aguiar RS ; Mitchell, MJ ; Teixeira, MM ; Vasconcelos Costa, V ; Frezard, F ; Guimaraes, PPG |
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Zeitschrift: | Nature communications, Jg. 15 (2024-01-18), Heft 1, S. 590 |
Veröffentlichung: | [London] : Nature Pub. Group, 2024 |
Medientyp: | academicJournal |
ISSN: | 2041-1723 (electronic) |
DOI: | 10.1038/s41467-024-44830-1 |
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