Modulation of lipid nanoparticle-formulated plasmid DNA drives innate immune activation promoting adaptive immunity.

ingentiumby ingentium

In Coronavirus Literature.

Publication date: Mar 13, 2025

Nucleic acid vaccines have grown in importance over the past several years, with the development of new approaches remaining a focus. We describe a lipid nanoparticle-formulated DNA (DNA-LNP) formulation which induces robust innate and adaptive immunity with similar serological potency to mRNA-LNPs and adjuvanted protein. Using an influenza hemagglutinin (HA)-encoding construct, we show that priming with our HA DNA-LNP demonstrated stimulator of interferon genes (STING)-dependent upregulation and activation of migratory dendritic cell (DC) subpopulations. HA DNA-LNP induced superior antigen-specific CD8 T cell responses relative to mRNA-LNPs or adjuvanted protein, with memory responses persisting beyond one year. In rabbits immunized with HA DNA-LNP, we observed immune responses comparable or superior to mRNA-LNPs at the same dose. In an additional model, a SARS-CoV-2 spike-encoding DNA-LNP elicited protective efficacy comparable to spike mRNA-LNPs. Our study identifies a platform-specific priming mechanism for DNA-LNPs divergent from mRNA-LNPs or adjuvanted protein, suggesting avenues for this approach in prophylactic and therapeutic vaccine development.

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Concepts Keywords
Dna adjuvanted protein
Efficacy antibody
Hemagglutinin DNA-LNP
Influenza lipid nanoparticle
Nanoparticle mRNA
plasmid DNA
T cell
vaccine

Semantics

Type Source Name
disease IDO protein
disease MESH influenza
disease IDO cell
disease MESH inflammation
drug DRUGBANK Ilex paraguariensis leaf
drug DRUGBANK Dihydroxy(oxo)molybdenum(6+)
drug DRUGBANK Azelaic acid
disease MESH Infection
drug DRUGBANK Esomeprazole
disease MESH COVID 19
pathway REACTOME Translation
disease IDO production
disease IDO immune response
drug DRUGBANK Hyaluronic acid
disease IDO process
disease MESH papillomatosis
drug DRUGBANK Tretamine
disease IDO assay
drug DRUGBANK Proline
disease IDO nucleic acid
drug DRUGBANK Phosphate ion
drug DRUGBANK BK-MDA
drug DRUGBANK Cycloserine
disease MESH tumor
drug DRUGBANK Coenzyme M
drug DRUGBANK Bisoprolol
drug DRUGBANK N-acetylsulfanilyl chloride
disease IDO blood
disease MESH weight loss
disease MESH morbidity
disease IDO facility
drug DRUGBANK Etoperidone
disease IDO pathogen
disease MESH infectious diseases
drug DRUGBANK Inosine
disease MESH Middle East respiratory syndrome
disease MESH cervical intraepithelial neoplasia
disease MESH Emerging Infectious Diseases
disease MESH Recurrent Respiratory Papillomatosis
drug DRUGBANK Pembrolizumab
disease MESH hepatocellular carcinoma
pathway KEGG Hepatocellular carcinoma
drug DRUGBANK Durvalumab
disease MESH Carcinoma
drug DRUGBANK Squalene
drug DRUGBANK Ibuprofen
pathway REACTOME Innate Immune System
disease MESH autoimmunity
drug DRUGBANK Pegademase bovine
disease MESH Allergy
disease MESH Death
drug DRUGBANK Diphenylpyraline
drug DRUGBANK Trestolone
disease MESH melanoma
pathway KEGG Melanoma
drug DRUGBANK Honey
drug DRUGBANK Biotin
disease IDO reagent
drug DRUGBANK Amlexanox
drug DRUGBANK Isoniazid
drug DRUGBANK Cholesterol
drug DRUGBANK Thymidine monophosphate
drug DRUGBANK Chromium
drug DRUGBANK Streptomycin
drug DRUGBANK Ethanol
drug DRUGBANK Polyethylene glycol
drug DRUGBANK Ammonium chloride
drug DRUGBANK Potassium
drug DRUGBANK Amino acids
drug DRUGBANK Dimethyl sulfoxide
drug DRUGBANK 2′-deoxyuridylic acid
drug DRUGBANK Activated charcoal
drug DRUGBANK Water
drug DRUGBANK Edetic Acid
drug DRUGBANK Sodium carbonate
drug DRUGBANK Sodium bicarbonate
drug DRUGBANK Alkaline Phosphatase
drug DRUGBANK Sodium phosphate monobasic
drug DRUGBANK Isoflurane
disease MESH AIDS
drug DRUGBANK Ketamine
drug DRUGBANK Xylazine

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