Title:An in silico Immunogenicity Analysis for PbHRH: An Antiangiogenic Peptibody by fusing HRH Peptide and Human IgG1 Fc Fragment
VOLUME: 15 ISSUE: 6
Author(s):Lin Ning, Jiang Huang *, Bifang He and Juanjuan Kang
Affiliation:Center for Informational Biology, University of Electronic Science and Technology of China, Chengdu, Center for Informational Biology, University of Electronic Science and Technology of China, Chengdu, Center for Informational Biology, University of Electronic Science and Technology of China, Chengdu, Center for Informational Biology, University of Electronic Science and Technology of China, Chengdu
Keywords:Peptibody, romiplostim, immunogenicity evaluation, MHC, IEDB.
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.
