IMMUNOINFORMATIC ANALYSIS OF A VACCINE CANDIDATE AGAINST T. CRUZI

TRINITARIO, SEBASTIÁN N.; DELFINO, MARÍA ALICIA; DZVONYK, POLINA; RUSSO, MELISSA; CARDOSO, ALEJANDRO C.; CERNY, NATACHA; MALCHIODI, EMILIO L.; SANCHEZ ALBERTI, ANDRÉS; BIVONA, AUGUSTO ERNESTO

Buenos Aires

Congreso; REUNIÓN ANUAL DE SOCIEDADES DE BIOCIENCIAS SAIC - SAI - SAFIS; 2021

BACKGROUND & AIMSChagas disease, caused by the infection of the protozoan parasite Trypanosoma cruzi, is a tropical neglected disease. To date, there is still no vaccine available against it. In this context, we have developed Traspain, a chimeric antigen containing domains of two T. cruzi relevant antigens: Cruzipain (Cz) and Amastigote Surface Protein-2 (ASP-2), bound by a linker alpha-helix. Traspain as a vaccine showed promising results in preclinical models. To broaden the understanding of Traspain as an immunological candidate, we have conducted in silico studies of its structure and immunological features.METHODSTraspain domains and epitopes conservation was evaluated by sequence alignment using Blast. Traspain tertiary structure was predicted with the novel algorithm RoseTTAFold. Most prevalent HLA alleles in Latin America and rest of the world were selected based on bibliography and IEDB. Subsequently, human T cell epitopes were predicted using artificial neural networks-based algorithms (NetMHCpan and NetMHCIIpan). Linear and discontinuous B cell epitopes were predicted using the servers BepiPred and DiscoTope respectively. To confirm antibody recognition, Western blot and ELISA employing a pool of human chagasic sera were assayed.RESULTSTraspain domains showed more than 80% of identity compared to representatives discrete typing units (DTUs) of T. cruzi. 119 nonapeptides were predicted as strong binders (SB) for HLA-I molecules covering the 62 most frequent alleles of world population. 69% of these potential epitopes are located within the ASP-2 domain. Regarding HLA-II molecules, 99 15-mer peptides were predicted as SB covering 95.8% of most frequent alleles. 38% of the predicted MHC-II epitopes are in the Cruzipain domain, 54% in the ASP-2 domain and 7% in the linker alpha-helix.15 continuous B-cell epitopes were predicted. Conformational B-cell epitopes were also successfully predicted. Antibody recognition of Traspain was confirmed by Western blot and ELISA using chagasic patients’ sera.CONCLUSIONImmuno-informatic analysis showed that Traspain sequence contains several potential human CTL, Th and B cell epitopes. Overall, these results support Traspain as a vaccine candidate to be tested in a first in human trial.