Immunoinformatics approach to epitope-based peptide vaccine design and receptor binding prediction for EIAV ENV polyprotein

A. SERGIO GARAY; ADRIANA SOUTULLO; CAROLINA VEAUTE; DANIEL E. RODRIGUES

Ciudad Autónoma de Buenos Aires

Congreso; XLIX Reunión Anual SAB; 2021

Sociedad Argentina de Biofísica

Equine infectious anemia virus (EIAV) is a lentivirus causing a persistent infection inhorses characterized by recurrent febrile episodes and high levels of viremia  ssociated with a novel antigenic strain of the virus. Retroviral envelope glycoproteins are synthesized as polyprotein precursors that are cleaved, during transport to the surface of infected cells, into the surface (SU-gp90) and transmembrane (TM-gp45) subunits, being the most antigenic viral proteins.In this report, we identified some novel T-cell (ELA-I, ELA-II) and B-cell epitopes within of the most antigenic EIAV ENV polyprotein with the potential to induce humoral and cell-mediated immunity, using a comprehensive set of immunoinformatics tools. In particular, we worked with American strains to propose an epitope-based peptide vaccine that involves our geographical zone as the main target. Two regions were found in SU-gp90 and 5 regions in TM-gp45 with great potential to be used as CD8+ peptide epitopes and 3 regions of SU-gp90 and 6 in TM-gp45 to be used as CD4 + epitopes. Eighteen B-cell regions had epitopes localized within both proteins,Taken together we selected those regions that contained B-cell and T-cell epitopes,localized between the following aminoacid residues 130-190; 430-530; 590-670 and700-790. The prediction of the transmembrane zones in TM-gp45 allowed to establish the probable location of the regions previously found as well as the fusion peptide.From the consensus sequences of each of the proteins, their 3D structure was modeled using the new machine learning-based algorithm, AlphaFold 2. Only a central region within SU-gp90 could be reliably modeled and was used for the prediction of conformational B epitopes. Since this region also contained the likely receptor binding region for EIAV, docking of this region with the Equine Lentivirus Receptor was performed to try to further delineate the shape of the binding site. In order to select the best docking pose, the predicted glycosylation sites were taken into account. The coiled-coil region of GP45 was also modeled but with a lower  confidence level.Our results were compared with experimental data from our own laboratory and also with those of other American researchers, taken from de Immuno Epitope Data Base (IEDB). Some of the epitopes found in this work are consistent with those previously reported, while others are new and will be used in the design of a new epitope-based vaccine.