EVALUATION OF LAST GENERATION ADJUVANTS ON IMMUNOGENICITY AND EFFICACY OF A PROTEIN SUBUNIT VACCINE CANDIDATE AGAINST TRYPANOSOMA CRUZI

DELFINO MARÍA ALICIA; TRINITARIO SEBASTIAN N; RUSSO MELISSA; DZVONYK POLINA; CARDOSO ALEJANDRO; CERNY NATACHA; MALCHIODI EMILIO L; BIVONA AUGUSTO E; SÁNCHEZ ALBERTI ANDRÉS

Congreso; REUNIÓN DE SOCIEDADES DE BIOCIENCIAS 2021; 2021

SAIC SAI AAFE NANOMED-AR

BACKGROUND AND AIMS:ChagasDisease is a potentially life-threatening illness caused by the protozoanparasite Trypanosoma cruzi. Currently there is no effective vaccine toprevent or treat the infection. Previously, we have developed Traspain, achimeric trivalent immunogen. To assess new adjuvants that might improve protectioninduced by vaccination, we evaluated the TLR3, TLR9 and STING ligands Poly(I:C), CpG oligodeoxynucleotide and Cyclic-di-AMP (CDA) respectively by thesubcutaneous route.METHODS:Groupsof 6-8 weeks old, female C3H mice (n=6/group) were vaccinated with 3 doses of 10µg of Traspain plus 25 µg of adjuvant or PBS as placebo. Exploratory bleedingwas performed and 20-30 days after the last dose, antigen specific immuneresponses were evaluated by ELISA, proliferation, and flow cytometry.Additionally, for efficacy assessment, immunized mice were challenged with theRA strain of T. cruzi (DTU VI). Parasitemia and weight loss wereemployed as readouts.RESULTS:SignificantTraspain-specific IgG levels were detected in sera from CDA and Poly(I:C)groups (IgG titres: 167117*, 60970* respectively, *p<0.01). Interestingly, CDA vaccinated sera exhibited 3- and25-times higher titres than Poly(I:C) or CpG (p<0.01).Interms of cell-mediated immunity, proliferation assays showed a significantdifference between Poly(I:C) and CDA vs placebo (p<0.05). Production of IL-2,TNF and IFNg was detected onthe CD4+ T cells subset upon protein recall. More than 60% of these cells correspondedto polyfunctional subsets in all groups, having CDA the highest level. Allformulations were able to reduce weight loss and parasitemia, resultingsignificant only in parasitemia for CDA and CpG vaccinated mice (p<0.05).CONCLUSIONS:Subcutaneousadministration of Traspain formulated with Poly(I:C), CpG or CDA is immunogenicand confers partial protection against T. cruzi. Traspain/CDA representsthe best combination in terms of both immunogenicity and anti-T. cruziefficacy.