Abstract:

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 celleliciting peptide AS15 (AVEIHRPVPGTAPPS) in C57BL/6J mice. Herein, we found that immunizingmice 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+ Tcell 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.

Published as:

El Bissati, K.; Krishack, P.A.; Zhou, Y.;Weber, C.R.; Lykins, J.; Jankovic, D.; Edelblum, K.L.; Fraczek, L.; Grover, H.; Chentoufi, A.A.; . P. Dubey , Steve Reed , Jeff Alexander , John Sidney , Alessandro Sette , Nilabh Shastri and Rima McLeod .CD4+ T Cell Responses to Toxoplasma gondii Are a Double-Edged Sword. Vaccines 2023, 11, 1485. https:// doi.org/10.3390/vaccines11091485