期刊
JOURNAL OF IMMUNOLOGY
卷 201, 期 7, 页码 1984-1993出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1800740
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资金
- Department of Laboratory Medicine, University of Washington
Tissue-resident memory CD8(+) T (Trm) cells in the liver are critical for long-term protection against pre-erythrocytic Plasmodium infection. Such protection can usually be induced with three to five doses of i.v. administered radiation-attenuated sporozoites (RAS). To simplify and accelerate vaccination, we tested a DNA vaccine designed to induce potent T cell responses against the SYVPSAEQI epitope of Plasmodium yoelii circumsporozoite protein. In a heterologous prime-and-trap regimen, priming using gene gun-administered DNA and boosting with one dose of RAS attracted expanding Ag-specific CD8(+) T cell populations to the liver, where they became Trm cells. Vaccinated in this manner, BALB/c mice were completely protected against challenge, an outcome not reliably achieved following one dose of RAS or following DNA-only vaccination. This study demonstrates that the combination of CD8(+) T cell priming by DNA and boosting with liver-homing RAS enhances formation of a completely protective liver Trm cell response and suggests novel approaches for enhancing T cell-based pre-erythrocytic malaria vaccines.
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