Mucosal vaccine based on trans-sialidase protects against acute and chronic damage after oral infection with Trypansosoma cruzi

PACINI MF; BULFONI BALBI C; DINATALE B; GONZALEZ F; FARRE C; CHAPO G; BOTTASSO O; CACIK PI; PROCHETTO E; MARCIPAR I; PEREZ A

Mar del Plata

Congreso; LXX Reunión Anual de la SAI, 16-19 noviembre de 2022; 2022

Sociedad Argentina de Inmunología

Oral Chagas disease is a frequent form of infection in some countries of Latin America. Although there are drugs for its treatment, currently there are no prophylactic vaccines to combat the disease. We previously showed that a nasal vaccine formulated with a N-terminal fragment of Trans-sialidase (TS) and combined with c-di-AMP(A) generated immunogenicity at mucosal and systemic levels, in terms of cellular and humoral response. Here, we evaluated prophylacticefficacy during acute (17 dpi) and chronic (110 dpi) phases. Thus,female BALB/c mice (n=4-7/group) were intranasal immunized (3 doses, one every 2 weeks). As control groups, we used mice not immunized (NI) or only treated with TS or c-di-AMP. After immunization, animals were orally challenged with 3000 Tulahuen strain/ mice (sub-lethal challenge). Parasitemia and clinical affectation (score) were recorded during the course of experiments. Muscle and liver damage (plasma CK, GOT, GPT) were assessed during the acute phase. Parasite load (qPCR), cytokines (TNF-α and INF-γ by ELISA and CBA) and myocarditis were evaluated at acute and chronic phases by histopathology. Heart functional impairment was evaluated by electrocardiogram (ECG) at 110 dpi. Clinical affectation, parasitemia and, acute muscle and hepatic damage were less evident in TS+A [e.g. GPT (17 dpi, AU, meanESM), Tc: 1880958, TS:12481200, TS+A 25035, NI 10725] compared to the rest of the groups (in all cases, p