Toxoplasma cyst wall CST9 elicits an acute-associated humoral response in humans and mice and protects against chronic infection in immunized mice

SALDARRIAGA CARTAGENA, ANA M.; RIVERA, ELIAS M.; SÁNCHEZ-LÓPEZ, EDWIN F.; FORMIGO, PAULA M.; LEGARRALDE, ARIEL; GANUZA, AGUSTINA; ALONSO, ANDRÉS M.; CLEMENTE, MARINA; ANGEL, SERGIO O.

MICROBIAL PATHOGENESIS

ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD

Año: 2025 vol. 205

0882-4010

AbstractBackgroundToxoplasma gondii is an obligate intracellular parasite that causes human and animal toxoplasmosis. It is considered an essential zoonotic foodborne infection. Up to now, there is not an adequate determination of acute toxoplasmosis in a single assay or a low-cost, safe vaccine against animal or human toxoplasmosis.MethodsWe selected three parasite proteins belonging to dense granules and present in the secretome: TGME49_200360 (hypothetical protein), GRA17, and CST9. These recombinant proteins were analyzed using serum from mice experimentally infected with Me49 cysts and using a panel of human sera grouped as acute, chronic, or seronegative by IgG-ELISA. Besides, C57BL mice were immunized with rCST9 combined with alum or PBS + alum and challenged with tachyzoite of RH (100) and Me49 (1000 and 10,000) strains. Survival, serology, and brain cysts were analyzed.ResultsOf the three proteins, only rCST9 showed reactivity with experimentally infected mice, restricted to day 15 post-infection but not on day 21 and beyond. Analysis of human serum samples showed that 36.66 % of acute sera and 4.61 % of chronic sera reacted with rCST9, while the other rAGs showed sensitivities below 5 % in all cases. The immunization of rCST9 combined with alum showed that it could not protect against the virulent strain RH but efficiently control the chronic infection in mice challenged with the avirulent strain Me49.ConclusionsThese data indicate that rCST9 presents an antigenic exposure restricted to the acute stage and can protect against chronic infection in the mouse model.