IMMUNOINFORMATIC ANALYSIS OF A VACCINE CANDIDATE AGAINST T. CRUZI

TRINITARIO, SEBASTIÁN NICOLÁS; MARIA ALICIA DELFINO; DZVONIK POLINA; MELISSA RUSSO; ALEJANDRO C CARDOSO LANDABURU; CERNY, NATACHA; EMILIO L MALCHIODI; SANCHEZ ALBERTI ANDRES; AUGUSTO E. BIVONA

Congreso; Reunión Anual de Sociedades de Biociencias; 2021

Chagas disease,caused by the infection of the protozoan parasite Trypanosoma cruzi, isa tropical neglected disease. To date, there is still no vaccine available againstit. In this context, we have developed Traspain, a chimeric antigen containingdomains of two T. cruzi relevant antigens: Cruzipain (Cz) and AmastigoteSurface Protein-2 (ASP-2). Traspain as a vaccine showed promising results in preclinicalmodels. To broaden the understanding of Traspain as an immunological candidate,we have conducted in silico studies of its structure and immunologicalfeatures.Traspain domains and epitopes conservation was evaluated by sequence alignmentusing Blast. Traspain structure was predicted with the novel algorithm RoseTTAFold.Most prevalent HLA alleles in Latin America and rest of the world were selectedbased on bibliography and IEDB. Subsequently, human T cell epitopes werepredicted using artificial neural networks-based algorithms (NetMHCpan and NetMHCIIpan).Linear and discontinuous B cell epitopes were predicted using the serversBepiPred and DiscoTope respectively. To confirm antibody recognition, Westernblot and ELISA employing a pool of human chagasic sera were assayed.Traspain domains showed more than 80% of identity compared to representatives discretetyping units (DTUs) of T. cruzi. 119 nonapeptideswere predicted as strong binders (SB) for HLA-I molecules covering the 62 mostfrequent alleles of world population. 69% of these potential epitopes are locatedwithin the ASP-2 domain. Regarding HLA-II molecules, 9915-mer peptides were predicted as SB covering 95.8% of most frequent alleles. 15 continuous B-cell epitopes were predicted. Conformational B-cell epitopeswere also successfully predicted. Antibody recognition was achieved.Immuno-informatic analysis showed that Traspain sequence contains several potentialhuman CTL, Th and B cell epitopes. Overall, these results support Traspain as avaccine candidate to be tested in a first in human trial.