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Peptide-TLR7/8a-Coordinated DNA Vaccines Elicit Enhanced Immune Responses against Infectious Diseases.
- Source :
-
ACS biomaterials science & engineering [ACS Biomater Sci Eng] 2024 Jul 08; Vol. 10 (7), pp. 4374-4387. Date of Electronic Publication: 2024 Jun 13. - Publication Year :
- 2024
-
Abstract
- DNA vaccines represent an innovative approach for the immunization of diverse diseases. However, their clinical trial outcomes are constrained by suboptimal transfection efficiency and immunogenicity. In this work, we present a universal methodology involving the codelivery of Toll-like receptor 7/8 agonists (TLR7/8a) and antigen gene using TLR7/8a-conjugated peptide-coated poly(β-amino ester) (PBAE) nanoparticles (NPs) to augment delivery efficiency and immune response. Peptide-TLR7/8a-coated PBAE NPs exhibit advantageous biophysical attributes, encompassing diminutive particle dimensions, nearly neutral ζ potential, and stability in the physiological environment. This synergistic approach not only ameliorates the stability of plasmid DNA (pDNA) and gene delivery efficacy but also facilitates subsequent antigen production. Furthermore, under optimal formulation conditions, the TLR7/8a-conjugated peptide coated PBAE NPs exhibit a potent capacity to induce robust immune responses. Collectively, this nanoparticulate gene delivery system demonstrates heightened transfection efficacy, stability, biodegradability, immunostimulatory effect, and low toxicity, making it a promising platform for the clinical advancement of DNA vaccines.
- Subjects :
- Animals
Humans
Mice
Female
Polymers chemistry
Plasmids genetics
Plasmids immunology
Mice, Inbred C57BL
Vaccines, DNA immunology
Vaccines, DNA administration & dosage
Toll-Like Receptor 8 immunology
Toll-Like Receptor 8 agonists
Toll-Like Receptor 7 agonists
Toll-Like Receptor 7 immunology
Nanoparticles chemistry
Peptides chemistry
Peptides immunology
Subjects
Details
- Language :
- English
- ISSN :
- 2373-9878
- Volume :
- 10
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- ACS biomaterials science & engineering
- Publication Type :
- Academic Journal
- Accession number :
- 38869358
- Full Text :
- https://doi.org/10.1021/acsbiomaterials.4c00749