In silico Design of Discontinuous Peptides Representative of B and T-cell Epitopes from HER2-ECD as Potential Novel Cancer Peptide Vaccines

Abstract

At present, the most common cause of cancer-related death in women is breast cancer. In a large proportion of breast cancers, there is the overexpression of human epidermal growth factor receptor 2 (HER2). This receptor is a 185 KDa growth factor glycoprotein, also known as the first tumor-associated antigen for different types of breast cancers. Moreover, HER2 is an appropriate cell-surface specific antigen for passive immunotherapy, which relies on the repeated application of monoclonal antibodies that are transferred to the patient. However, vaccination is preferable because it would stimulate a patient's own immune system to actively respond to a disease. In the current study, several bioinformatics tools were used for designing synthetic peptide vaccines. PEPOP was used to predict peptides from HER2 ECD subdomain III in the form of discontinuous-continuous B-cell epitopes. Then, T-cell epitope prediction web servers MHCPred, SYFPEITHI, HLA peptide motif search, Propred, and SVMHC were used to identify class-I and II MHC peptides. In this way, PEPOP selected 12 discontinuous peptides from the 3D structure of the HER2 ECD subdomain III. Furthermore, T-cell epitope prediction analyses identified four peptides containing the segments 77 (384-391) and 99 (495-503) for both B and T-cell epitopes. This work is the only study to our knowledge focusing on design of in silico potential novel cancer peptide vaccines of the HER2 ECD subdomain III that contain epitopes for both B and T-cells. These findings based on bioinformatics analyses may be used in vaccine design and cancer therapy; saving time and minimizing the number of tests needed to select the best possible epitopes.

Benchmarking the PEPOP methods for mimicking discontinuous epitopes

“…PEPOP has been or can be used for all the purposes where surrogate epitopes are needed, purposes such as those cited by Van Regenmortel, i.e. “seeking vaccine candidates” [49] or “replacing Ags in diagnostic immunoassays”. It can also efficiently help in mapping epitopes [33–35] (Duarte C et al, A mimic of a discontinuous epitope from AaH II identified by combining wet and dry experiments: a new experimental methodology to localize discontinuous epitopes, in preparation; Abraham J-D et al, Combination of bioinformatics and experimental approaches to map the conformational epitope on GM-CSF, in preparation) and would be a very informative tool for understanding the rules of molecular mimicry, a very difficult [23, 41, 50] but promising research field as testified by the number of available studies [9, 51–54] and tools [30, 55, 56].…”

“…Although some studies begin to explore this problem [47] the proposed benchmark is not applicable for all epitope prediction tools neither for all studies. Anyway, PEPOP has already been successfully used in several studies of different goals [27, 32–35, 48, 49].…”

Benchmarking the PEPOP methods for mimicking discontinuous epitopes

“…Although some studies begin to explore this problem [47] the proposed benchmark is not applicable for all epitope prediction tools neither for all studies. Anyway, PEPOP has already been successfully used in several studies of different goals [27,[32][33][34][35]48,49]. Van Regenmortel, i.e.…”

“…Van Regenmortel, i.e. "seeking vaccine candidates" [49] or "replacing antigens in diagnostic immunoassays". It can also efficiently help in mapping epitopes [33][34][35]50,51] and would be a very informative tool for understanding the rules of molecular mimicry, a very difficult [23,41,52] but promising research field as testified by the number of available studies [9,[53][54][55][56] and tools [30,57,58].…”

Epitope Prediction by Novel Immunoinformatics Approach: A State-of-the-art Review

“…Tables 1, 2 and 3 show the results of our studies in the frequency of each software for prediction of conformational epitopes of B cell according to the nature of the antigen evaluated in the three sections of viral, bacterial 3 The assortment of articles for epitope prediction of bacterial antigens (4 articles out of 50 articles) Their related web tools have been shown in the second column. In the third and fourth columns, the frequency and percentage of the regularity of each web tool in articles are shown a Three cases of 50 articles were studied for prediction of MHC Class I epitopes b Three cases of 50 articles were studied for prediction of MHC Class II epitopes c Four articles were studied on discontinuous B-cell epitope prediction d Three articles were studied on continuous B-cell epitope prediction Nezafat et al (2014), Manijeh et al (2013), Mahdavi et al (2012) and Mahdavi and Moreau (2016) and tumor-specific antigens. Based on our investigations, Discotope and Ellipro softwares are most widely used for predicting conformational viral B cell epitopes and Discotope software is most widely used for predicting bacterial conformational B cell epitopes and predicting tumor-specific B cell epitopes.…”