Mucosal vaccine based in a fragment of recombinant trans-sialidase protects against experimental oral Chagas disease

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

Buenos Aires

Congreso; LXVI Reunión Anual de la SAIC, 17-20 noviembre de 2021; 2021

Sociedad Argentina de Investigación Clínica

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. Here, we evaluated the immunogenicity and prophylactic efficacy against oral infection generated by a N-terminal recombinant fragment of Trans-sialidase (TSNt), containing different B and T epitopes confirmed by bioinformatics. For mucosal immunization, 10μg ofTSNt was combined with different adjuvants: c-di-AMP(A) or ISPA(I). Thus, female BALB/c mice (n=6/group) were immunized intranasally (3 doses, one every 2 weeks). As control groups we used mice not immunized (NI) or only treated with TSNt. To evaluate the immunogenicity, 15 days after the last immunization, we performed an in vivo cell-mediated test (delayed hypersensitivity test, DHT), splenic multifunctional T cell (IFNγ+/RORγt+) detection by flow cytometryafter in vitro stimulation with TSNt, and specific humoral response by ELISA. Next, we evaluated prophylactic efficacy during acute phase. Thus, animals were orally challenged with 3000 Tulahuen strain/mice (sub-lethal challenge). Parasitemia, clinical affectation (score), muscle and liver damage (plasma CK, GOT, GPT) was also assessed. In terms of immunogenicity, TSNt+A and TSNt+I vaccines developed an enhanced DHT until 72 h, compared to control groups(in all cases, p