期刊
VACCINES
卷 11, 期 9, 页码 -出版社
MDPI
DOI: 10.3390/vaccines11091485
关键词
Toxoplasma gondii; HLA-A*11:01; vaccine; TLR4; CD4(+) T cells
CD4(+) T cells play critical roles in controlling Toxoplasma infection. The combination of AS15 and GLA-SE can protect mice against Toxoplasma parasites, but can also cause severe pathology. The introduction of PADRE reverses the harmful effects of AS15.
CD4(+) T cells have been found to play critical roles in the control of both acute and chronic Toxoplasma infection. Previous studies identified a protective role for the Toxoplasma CD4(+) T cell-eliciting peptide AS15 (AVEIHRPVPGTAPPS) in C57BL/6J mice. Herein, we found that immunizing mice with AS15 combined with GLA-SE, a TLR-4 agonist in emulsion adjuvant, can be either helpful in protecting male and female mice at early stages against Type I and Type II Toxoplasma parasites or harmful (lethal with intestinal, hepatic, and spleen pathology associated with a storm of IL6). Introducing the universal CD4(+) T cell epitope PADRE abrogates the harmful phenotype of AS15. Our findings demonstrate quantitative and qualitative features of an effective Toxoplasma-specific CD4(+) T cell response that should be considered in testing next-generation vaccines against toxoplasmosis. Our results also are cautionary that individual vaccine constituents can cause severe harm depending on the company they keep.
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