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A DNA vaccine (EG95-PT1/2/3-IL2) encoding multi-epitope antigen and IL-2 provokes efficient and long-term immunity to echinococcosis.
- Source :
-
Journal of Controlled Release . Sep2023, Vol. 361, p402-416. 15p. - Publication Year :
- 2023
-
Abstract
- Echinococcosis is a highly prevalent global zoonosis, and vaccines are required. The commercial vaccine based on a protein-based subunit (EG95), however, is limited by its insufficient cellular immunity, a short protection period, and limited prevention against novel mutant strains. Herein, we applied bioinformatics to develop a DNA vaccine (pEG95-IL2) expressing both multi-epitope-based antigens (EG95-PT1/2/3) and an IL-2 adjuvant to regulate T cell differentiation and memory cell response. EG95-PT1/2/3 was screened with hierarchical structure prediction from the epitope conformation of B cells with high confidence across various species to guarantee immunogenicity. Importantly, cationic arginine-rich lipid nanoparticles (RNP) were utilized as a delivery vehicle to form lipoplexes that had a transfection efficiency of nearly two orders of magnitude greater than that of commercial reagents (Lipofectamine 2000 and polyethyleneimine) with both immune and nonimmune cells (DC2.4 and L929 cells, respectively). RNP/pEG95-IL2 lipoplexes displayed a robust and long-term antigen expression, as well as adjuvant effects during the immunization. Consequently, intramuscular injection of RNP/pEG95-IL2 elicited similar humoral immune responses and significantly greater cellular responses in mice when compared with those of the commercial vaccine. In addition, the inoculation protocol of RNP/pEG95-IL2 with sequential booster further strengthens cellular immunity in comparison with the homologous booster. Those findings provide a promising strategy for improving plasmid vaccine efficacy. [Display omitted] • Multi-epitope-based DNA vaccine (RNP/pEG95-IL2) was developed by bioinformatics technology. • RNP/pEG95-IL2 elicited stronger cellular immune responses compared to the commercial vaccine. • The SB strategy of DNA vaccine produced greater immune responses than HB. • RNP benefited high and long-lasting expression of DNA antigens. • RNP accelerated BMDCs maturation and cytokine production as an immune adjuvant. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01683659
- Volume :
- 361
- Database :
- Academic Search Index
- Journal :
- Journal of Controlled Release
- Publication Type :
- Academic Journal
- Accession number :
- 171829909
- Full Text :
- https://doi.org/10.1016/j.jconrel.2023.07.047