Nanoparticle-based DNA vaccine protects against SARS-CoV-2 variants in female preclinical models.

Nanoparticle-based DNA vaccine protects against SARS-CoV-2 variants in female preclinical models.

Publication date: Jan 18, 2024

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.

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Concepts Keywords
Dna Cov
Library Effective
Long Hps
Nanoparticle Lnp
Vaccine Lnps
Models
Pdna
Protection
Safe
Sars
Vaccine
Variants
Vocs

Semantics

Type Source Name
disease VO DNA vaccine
disease VO effective
disease VO vaccine
disease IDO cell
disease VO COVID-19 vaccine
disease VO vaccine candidate
disease MESH COVID 19
pathway REACTOME Immune System
disease VO Viruses
drug DRUGBANK Inosine
disease VO dose
disease VO immunization
disease IDO production
drug DRUGBANK Cholesterol
disease VO organ
disease VO injection
disease VO efficiency
disease VO viability
drug DRUGBANK Tretamine
disease IDO assay
drug DRUGBANK Albendazole
drug DRUGBANK Isopropyl Alcohol
disease VO vaccine efficacy
disease VO vaccinated
drug DRUGBANK Ethanol
disease VO immunized
disease VO vaccination
disease MESH weight loss
disease MESH infection
disease VO Glycoprotein
drug DRUGBANK Glycine
disease MESH edema
disease MESH interstitial pneumonia
disease VO titer
drug DRUGBANK Filgrastim
disease VO ANOVA
drug DRUGBANK Proline
drug DRUGBANK Polyethylene glycol

Original Article

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