Immunoinformatics Analysis Reveals Potential Immunogenic Cores of Experimentally Validated B-Cell Epitopes of the Human Amyloid-Beta Precursor Protein

Abstract

Synthetic peptide immunogens based on B-cell epitopes from protein antigens are key to peptide vaccine design. Experimentally validated epitopes can be quite long, and not all residues might be significant for binding. Immunogenic cores can be identified so synthesis will focus on the relevant amino acid sequences. An immunoinformatics approach was done using online servers such as AllerTOP v.2, VaxiJen, IEDB, and Protein-Sol to evaluate the allergenicity, antigenicity, flexibility, accessibility, hydrophilicity, and solubility of B-cell epitope sequences of HAPP (Human Amyloid-Beta Precursor Protein). The immunogenic sequences underwent docking using GalaxyPepDock and validation using MolProbity, while PRODIGY was used to determine the binding energies of the identified sequences with select antibodies. Five immunogenic cores were determined: ⁶⁸²EVHH⁶⁸⁵ was identified via structure similarity, ⁶⁷⁵FRHDSGY⁶⁸¹ and ⁶⁹⁴DVGSNKG⁷⁰⁰ via flexibility analysis, and ⁶⁷⁵FRHDSGYEVHH⁶⁸⁵ and ⁶⁹⁴DVGSNK⁶⁹⁹ identified via surface accessibility All immunogenic cores exhibited spontaneous binding with antibodies, and also demonstrated comparable or even increased binding strength compared with the source epitope. These findings suggest that there are potential immunogenic cores found in HAPP, which can be potentially used for more efficient peptide vaccine design.