An in silico Immunogenicity Analysis for PbHRH: An Antiangiogenic Peptibody by fusing HRH Peptide and Human IgG1 Fc Fragment

Author(s): Lin Ning, Jiang Huang*, Bifang He, Juanjuan Kang.

Journal Name: Current Bioinformatics

Volume 15 , Issue 6 , 2020

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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.

Conclusions: 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.

Keywords: Peptibody, romiplostim, immunogenicity evaluation, MHC, IEDB.

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Article Details

VOLUME: 15
ISSUE: 6
Year: 2020
Page: [556 - 561]
Pages: 6
DOI: 10.2174/1574893614666190730104348
Price: $95

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