EARLY TARGETING OF MYELOID-DERIVED SUPPRESSOR CELLS IMPROVES THE PROTECTIVE CAPACITY OF TSf-ISPA VACCINE AGAINST TRYPANOSOMA CRUZI

GAMBA, JUAN CRUZ; PROCHETTO, ESTEFANÍA; LUPI, GIULIANA; BONTEMPI, IVÁN; GONZÁLEZ FLORENCIA; PACINI FLORENCIA; CAROLINA PONCINI; VERMEULEN, MÓNICA; PÉREZ, ANA ROSA; MARCIPAR, IVÁN; CABRERA, GABRIEL

Congreso; REUNIÓN DE SOCIEDADES DE BIOCIENCIAS 2020; 2020

Introduction: We have previously reported that immunization witha trans-sialidase-based antigen (TSf) formulated with a cage-likeparticle adjuvant (ISPA) confers protection against Trypanosomacruzi (T.cruzi). It has been shown that myeloid-derived suppressorcells (MDSCs) notably increase in several organs during mice acuteinfection.Aim: to study whether MDSC depletion could further improve theefficacy of the TSf-ISPA vaccine candidate against T.cruzi.Methods: 3 subcutaneous doses of TSf-ISPA were given to BALB/cmice before intraperitoneal infection with 1000 Tulahuen trypomastigotes.5-fluorouracil (5FU) (50mg/kg) was given at different times(prior or during infection) to deplete MDSCs. Parasitemia was monitoredat days 14 and 21 postinfection (p.i.). Survival was assesseduntil day 40 p.i. Flow cytometry was used to measure the % andnumber of MDSCs (CD11b+ GR-1+), CD4 and CD8 T cells, B cellsand CD11chigh dendritic cells in the spleen after 5FU treatment.Results: Survival after infection was always higher in TSf-ISPA-immunizedand infected mice (TSf-ISPA Tc+ group) than control infectedPBS-treated mice (PBS Tc+ group) (p