DOUBLE 5-FLUOROURACIL ADMINISTRATION POTENTIATES A TRANS-SIALIDASE-BASED VACCINE AGAINST TRYPANOZOMA CRUZI

BORGNA ELIANA1, ; ESTEFANÍA PROCHETTO; GAMBA JUAN CRUZ; PÉREZ ANA ROSA; GONZÁLEZ FLORENCIA; MARCIPAR, IVÁN1, CABRERA GABRIEL

San Luis

Congreso; LXXI Reunión Científica Anual de la Sociedad Argentina de Inmunología SAI; 2023

Introduction: Trypanosoma cruzi (T. cruzi) is the etiological agent of Chagasdisease, a tropical neglected illness for which a licensed vaccine is stillunavailable. We previously described a vaccine candidate composed of a transsialidasefragment (TSf) and a cage-like particle adjuvant (ISPA). In addition,depletion of myeloid-derived suppressor cells (MDSCs) using one or two dosesof 5-fluorouracil (5FU) during immunization enhanced the efficacy of the vaccineformulation.Objective: to characterize the impact of one versus two doses of 5FU on thekinetics of MDSCs during a two-week period following TSf-ISPA immunization,and to compare the efficacy of both protocols against high-dose challenges of T.cruzi.Methods: BALB/c mice were given 3 doses of TSf-ISPA, with a 15-day intervalbetween each dose. For mice receiving the 5FU-TSf-ISPA treatment, a singledose of 5FU (50mg/kg) was administered one day before each immunization. Inthe case of DOUBLE 5FU-TSf-ISPA treatment, 5FU was given one day beforeand eight days after each immunization dose. Flow cytometry was used tomeasure CD11b+GR-1+ MDSCs in splenocytes (suppressive capacity alreadycontrolled) on days 2, 7, and 15 following the final immunization dose.Additionally, mice were intraperitoneally infected with Tulahuen T. cruzi in varyingdoses (1500, 2000, 3000). Parasitemia were monitored on different days’ postinfection(p.i.), and survival rates were assessed until day 40 (p.i.).Results: At days 2 and 7 post-immunization (p.imm), both 5FU-TSf-ISPA andDOUBLE 5FU-TSf-ISPA mice exhibited similar percentage and absolute numberof CD11b+Gr-1+ MDSCs splenocytes. Conversely, by day 15 p.imm, theDOUBLE 5FU-TSf-ISPA group displayed a reduced percentage and absolutenumber of CD11b+Gr-1+ MDSCs compared to 5FU-TSf-ISPA mice. Meanpercentage ±standard deviation (SD): 5FU-TSf-ISPA 11,6±0.8; DOUBLE 5FUTSf-ISPA 3,2±1,3 (p