Immunogenicity and protective efficacy of anti-T. cruzi nasal vaccine prototypes based on Transialidase

PACINI, M.F.; GONZÁLEZ, F.; VILLAR, S.; FARRÉ, C.; CABRAL, N.; DA SILVA, O.; BARBOSA, E.; CHAPO, G.; GABRIEL CABRERA; BONTEMPI, I.; ESTEFANÍA PROCHETO; ESPARIZ, MARTIN; BLANCATO, VÍCTOR S.; MAGNI, CHRISTIAN; MARCIPAR, I.; PÉREZ, A.R.

Mar del Plata

Encuentro; LXVI Reunión Anual de la Sociedad Argentina de Inmunología; 2018

SAI-SAIC-SAFIS

Currently there is not available a prophylactic vaccine for Chagas disease. Therefore, in this work we evaluated whether the administration of different nasal vaccine prototypes could prevent the development of T. cruzi (Tc) infection through the induction of specific andsystemic immune response. A fragment from the immunodominant parasite antigen called transialidase (TSf), containing both B and T epitopes was selected by bioinformatics. TSf was expressed in a L. lactis recombinant strain and then purified, avoiding the presence of endotoxins like LPS in vaccine formulations. Thus, female Balb/c mice (n= 5-6/group) were immunized by intranasal route (three doses, one every two weeks) with different vaccine formulations combining TSf with different adjuvants (c-di-AMP or ISPA).We also assayed the whole recombinant L. lactis expressing TSf as delivery system plus c-di-AMP (LL-TSf+c-di-AMP). Non immunized mice were used as control group (Co). In immunized mice, humoral and cellular immune responses were assayed prior to infection. After oral infection with 2500 Tc/mice (Tulahuen strain), the parasitemia and the clinical score were determined. Intranasal immunized mice with TSf+c-di-AMP showed enhanced levels of IgG2a and IgG1 compared to TSf and Co groups (in all cases, p<0.05). TSf+ISPAand LL-TSf+c-di-AMP immunized mice also tend to increase both TSf-specific-antibodies compared to Co and TSf. TSf+c-di-AMP immunized mice and, in a lesser extent TSf+ISPA, elicited a higher TS-specific cellular mediated immune response after 24 and 48 h (DHT in footpads). Parasite load after 14 and 28 days post-infection was less evident in TSf+c-di-AMP animals compared with the rest of the groups. Moreover, TSf+c-di-AMP animals exhibited less clinical affectation (clinical global score, p<0.05 vs. all groups). Taken together, these results indicate that TSf+c-di-AMP and TSf+ISPA formulations tested in this work would be good candidates for the development of a prophylactic mucosal vaccine against T. cruzi.