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.

背景：肽体是肽和抗体的混合体，代表了一种新的治疗用途。以前，我们通过计算设计了一种抗血管生成肽抗体PbHRH，它以Romiplostim为模板融合了具有抑制血管生成作用的HRH肽和人IgG1 Fc片段。分子建模和模拟结果表明，它将是治疗那些与血管生成有关的病理性疾病的潜在药物。但是，其免疫原性尚不清楚。

方法：使用几种生物信息学工具来预测潜在的表位，以评估PbHRH的免疫原性。将Romiplostim设置为控件。推荐使用IEDB方法进行MHC-1和MHC-II结合预测，并使用IEDB Web服务器（http://tools.iedb.org/immunogenicity/）确定每种肽的MHC-1免疫原性。

结果：在这项工作中，预测某些肽具有潜在的能力，可结合PbHRH和Romiplostim中的MHC-I和MHC-II分子作为潜在表位。这些选定的肽大多数都完全相同。等位基因频率分析显示人群分布低。结合MHC-1免疫原性预测分析，HRH和PbHRH均显示低免疫原性。

结论：使用生物信息学工具预测了一些可能与MHC-I和MHC-II分子结合的潜在表位。与Romiplostim的比较分析和MHC-1免疫原性预测结果表明，HRH和PbHRH的免疫原性均较低。因此，我们形成了一种策略，以评估肽抗体的免疫原性，以进行未来的改进。