IMMUNOINFORMATIC ANALYSIS OF A VACCINE CANDIDATE AGAINST T. CRUZI

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

Congreso; REUNIÓN DE SOCIEDADES DE BIOCIENCIAS 2021; 2021

SAIC SAI AAFE NANOMEDar

Chagas disease, caused by the infection of the protozoan parasiteTrypanosoma cruzi, is a tropical neglected disease. To date,there is still no vaccine available against it. In this context, wehave developed Traspain, a chimeric antigen containing domainsof two T. cruzi relevant antigens: Cruzipain (Cz) and AmastigoteSurface Protein-2 (ASP-2). Traspain as a vaccine showed promisingresults in preclinical models. To broaden the understandingof Traspain as an immunological candidate, we have conductedin silico studies of its structure and immunological features.Traspain domains and epitopes conservation was evaluated bysequence alignment using Blast. Traspain structure was predictedwith the novel algorithm RoseTTAFold. Most prevalent HLA allelesin Latin America and rest of the world were selected basedon bibliography and IEDB. Subsequently, human T cell epitopeswere predicted using artificial neural networks-based algorithms(NetMHCpan and NetMHCIIpan). Linear and discontinuous B cellepitopes were predicted using the servers BepiPred and DiscoToperespectively. To confirm antibody recognition, Western blot andELISA employing a pool of human chagasic sera were assayed.Traspain domains showed more than 80% of identity comparedto representatives discrete typing units (DTUs) of T. cruzi. 119nonapeptides were predicted as strong binders (SB) for HLA-Imolecules covering the 62 most frequent alleles of world population.69% of these potential epitopes are located within theASP-2 domain. Regarding HLA-II molecules, 99 15-mer peptideswere predicted as SB covering 95.8% of most frequent alleles.15 continuous B-cell epitopes were predicted. ConformationalB-cell epitopes were also successfullypredicted. Antibody recognition was achieved.Immuno-informatic analysis showed that Traspain sequence containsseveral potential human CTL, Th and B cell epitopes. Overall, these results support Traspain as a vaccine candidate to be testedin a first in human trial.