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,; GONZÁLEZ FB; FARRE CECILIA

Congreso; Reunión anual de Sociedades de Biociencias SAI, SAIC Y SAFIS 2022.; 2022

Oral Chagas disease is a frequent form of infection in some countriesof Latin America. Although there are drugs for its treatment, currentlythere are no prophylactic vaccines to combat the disease. Wepreviously showed that a nasal vaccine formulated with a N-terminalfragment of Trans-sialidase (TS) and combined with c-di-AMP(A)generated immunogenicity at mucosal and systemic levels, in termsof 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 (3doses, one every 2 weeks). As control groups, we used mice notimmunized (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. Muscleand liver damage (plasma CK, GOT, GPT) were assessed duringthe acute phase. Parasite load (qPCR), cytokines (TNF-α and INF-γby ELISA and CBA) and myocarditis were evaluated at acute andchronic phases by histopathology. Heart functional impairment wasevaluated by electrocardiogram (ECG) at 110 dpi. Clinical affectation,parasitemia and, acute muscle and hepatic damage were lessevident in TS+A [e.g. GPT (17 dpi, AU, meanESM), Tc: 1880958,TS:12481200, TS+A 25035, NI 10725] compared to the rest of thegroups (in all cases, p