期刊
NPJ VACCINES
卷 2, 期 -, 页码 -出版社
SPRINGERNATURE
DOI: 10.1038/s41541-017-0024-6
关键词
-
资金
- Engel
- Pritzker
- Rosenthal
- National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services [DMID-NIAID U01 AI77887, R01 AI027530, U19 AI110819]
- Knights Templar Eye Foundation
- Research to Prevent Blindness Foundation
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [U19AI110819, U01AI077887] Funding Source: NIH RePORTER
We designed and produced a self-assembling protein nanoparticle. This self-assembling protein nanoparticle contains five CD8(+) HLA-A03-11 supertypes-restricted epitopes from antigens expressed during Toxoplasma gondii's lifecycle, the universal CD4(+) T cell epitope PADRE, and flagellin as a scaffold and TLR5 agonist. These CD8(+) T cell epitopes were separated by N/KAAA spacers and optimized for proteasomal cleavage. Self-assembling protein nanoparticle adjuvanted with TLR4 ligand-emulsion GLA-SE were evaluated for their efficacy in inducing IFN-gamma responses and protection of HLA-A* 1101 transgenic mice against T. gondii. Immunization, using self-assembling protein nanoparticle-GLA-SE, activated CD8(+) T cells to produce IFN-gamma. Self-assembling protein nanoparticle-GLA-SE also protected HLA-A* 1101 transgenic mice against subsequent challenge with Type II parasites. Hence, combining CD8(+) T cell-eliciting peptides and PADRE into a multi-epitope protein that forms a nanoparticle, administered with GLA-SE, leads to efficient presentation by major histocompatibility complex Class I and II molecules. Furthermore, these results suggest that activation of TLR4 and TLR5 could be useful for development of vaccines that elicit T cells to prevent toxoplasmosis in humans.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据