A Live Attenuated AP2X-1-Deficient Toxoplasma Strain Confers Protective Immunity Against Acute and Chronic Toxoplasmosis in a Murine Model
TL;DR
PruΔap2X-1 represents a potential live-attenuated vaccine candidate against toxoplasmosis, with a favorable safety profile observed under the experimental conditions, and induces a strong Th1-biased cellular and humoral immune response.
Abstract
Simple Summary Toxoplasmosis, caused by the zoonotic parasite Toxoplasma gondii, is a major concern for immunocompromised individuals and the livestock industry. Research has shown that AP2X-1 is important for growth, conversion between tachyzoites and bradyzoites, and sexual stage development of T. gondii. In the present study, we found that all mice infected with the PruΔap2X-1 knockout strain survived even at the highest dose (5 × 106 tachyzoites), and no brain cysts were detected. Vaccinated mice were fully protected against both acute disease caused by the type II Pru and ToxoDB#9 PYS strains, and chronic infection induced by tissue cysts, whereas vaccinated mice had modestly extended survival time without conferring complete protection against challenge with the highly virulent RH strain. Moreover, vaccination induced a strong Th1-biased cellular and humoral immune response. Thus, PruΔap2X-1 represents a potential live-attenuated vaccine candidate against toxoplasmosis, with a favorable safety profile observed under the experimental conditions.