An In Silico Immunogenicity Analysis for PbHRH: An Antiangiogenic Peptibody by Fusing HRH Peptide and Human IgG1 Fc Fragment

Abstract

Background: Peptibodies, the hybrid of peptides and antibodies, represent a novel strategy in therapeutic use. Previously, we computationally designed an antiangiogenic peptibody PbHRH, which fused the HRH peptide with angiogenesis-suppressing effect and human IgG1 Fc fragment using Romiplostim as template. Molecular modeling and simulation results indicated that it would be a potential drug for the treatment of those angiogenesis related pathological disorders. However, its immunogenicity is not known. Methods: Several bioinformatics tools are used to predict the potential epitopes for the evaluation of the immunogenicity of PbHRH. Romiplostim is set as the control. IEDB-recommended method is used in MHC-I and MHC-II binding prediction, and the IEDB web server (http://tools.iedb.org/immunogenicity/) is used to determine the MHC-I immunogenicity of each peptide. Results: In this work, some peptides are predicted to have the potential ability to bind to MHC-I and MHC-II molecules both in PbHRH and Romiplostim as the potential epitopes. Most of these selected peptides are exactly the same. Allele frequency analysis shows a low population distribution. Combined with the analysis of MHC-I immunogenicity prediction, both HRH and PbHRH show low immunogenicity. Conclusion: Some potential epitopes which could bind to both MHC-I and MHC-II molecules are predicted using bioinformatics tools. The comparative analysis with Romiplostim and the results of MHC-I immunogenicity prediction indicate the low immunogenicity of both HRH and PbHRH. Thus, we form a strategy to evaluate the immunogenicity of peptibodies for the future improvement.