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, antiangiogenic.
Graphical Abstract
[http://dx.doi.org/10.1016/j.bmc.2017.06.052] [PMID: 28720325]
[PMID: 30129406]
[http://dx.doi.org/10.1016/j.copbio.2009.10.010] [PMID: 19889530]
[http://dx.doi.org/10.1073/pnas.1603335113] [PMID: 27114517]
[http://dx.doi.org/10.1038/nrd2741] [PMID: 18974747]
[http://dx.doi.org/10.1080/14712598.2017.1296131 PMID: 28274140]
[http://dx.doi.org/10.1517/13543784.2011.549125] [PMID: 21210755]
[http://dx.doi.org/10.1016/j.cellsig.2007.05.013] [PMID: 17658244]
[http://dx.doi.org/10.1038/sigtrans.2017.10] [PMID: 29263914]
[http://dx.doi.org/10.7150/ijbs.24582] [PMID: 29989101]
[http://dx.doi.org/10.2174/1389203718666170828123449 PMID: 28847291]
[http://dx.doi.org/10.1080/14740338.2016.1218467 PMID: 27551882]
[http://dx.doi.org/10.1254/jphs.CR0070056] [PMID: 18094522]
[http://dx.doi.org/10.1186/s13073-016-0288-x] [PMID: 27029192]
[http://dx.doi.org/10.1093/bioinformatics/btv639] [PMID: 26515819]
[http://dx.doi.org/10.1186/1471-2105-6-132] [PMID: 15927070]
[http://dx.doi.org/10.1186/1471-2105-10-394] [PMID: 19948066]
[http://dx.doi.org/10.1186/1745-7580-4-2] [PMID: 18221540]
[http://dx.doi.org/10.1093/bioinformatics/btp137] [PMID: 19297351]
[http://dx.doi.org/10.1007/s00251-011-0579-8] [PMID: 22009319]
[http://dx.doi.org/10.4049/jimmunol.1600582] [PMID: 27402703]
[http://dx.doi.org/10.1007/s00018-005-4528-2] [PMID: 15868101]
[http://dx.doi.org/10.1038/nbt1215] [PMID: 16767078]
[http://dx.doi.org/10.1093/nar/gku938] [PMID: 25300482]
[http://dx.doi.org/10.1186/1471-2105-11-568] [PMID: 21092157]
[http://dx.doi.org/10.1371/journal.pcbi.1000048] [PMID: 18389056]
[http://dx.doi.org/10.1007/s00251-015-0873-y] [PMID: 26416257]
[http://dx.doi.org/10.1186/1471-2105-10-296] [PMID: 19765293]
[http://dx.doi.org/10.1186/1471-2105-8-238] [PMID: 17608956]
[http://dx.doi.org/10.1038/9858] [PMID: 10385319]
[http://dx.doi.org/10.1371/journal.pcbi.1003266] [PMID: 24204222]
[http://dx.doi.org/10.1007/s00726-005-0289-3] [PMID: 16622600]
[http://dx.doi.org/10.1002/bip.23095] [PMID: 29266205]
[http://dx.doi.org/10.4161/mabs.21024] [PMID: 22820181]
[http://dx.doi.org/10.1016/j.coph.2008.06.002] [PMID: 18602024]
[http://dx.doi.org/10.1002/pbc.20972] [PMID: 16933266]
[http://dx.doi.org/10.2174/0929867311320150005] [PMID: 23317161]
[http://dx.doi.org/10.1007/s002510050595] [PMID: 10602881]
[http://dx.doi.org/10.4049/jimmunol.1700893] [PMID: 28978689]
[http://dx.doi.org/10.1038/ng.3576] [PMID: 27213287]