Abstract

SUPPLEMENTARY MATERIALS : FIGURE S1: Cartoon model showing the conceptual advance provided by this work.DATA AVAILABILITY STATEMENT : Data sharing is not applicable to this article.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 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.The Division of Intramural Research of the National Institute of Allergy and Infectious Diseases of the National Institutes of Health.https://www.mdpi.com/journal/vaccinesam2023Medical MicrobiologyNon

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