Designing of Epitope-Focused Vaccine by Targeting E6 and E7 Conserved Protein Sequences: An Immuno-Informatics Approach in Human Papillomavirus 58 Isolates

Abstract

Human papillomavirus (HPV) is a DNA virus that belongs to the papillomavirus family and is capable of infecting humans. Currently, few vaccines are available to prevent infection by HPV. However, they are not so much effective and provide little benefit to women who have already been infected with HPV. The aim of this study was to design epitope-based vaccines of HPV58 by targeting E6 and E7 proteins of HPV58. Proteomic sequences were retrieved from different isolates at different time periods and later analyzed by performing alignment of these sequences. To ensure the capacity of humoral and cell-mediated immunity, both B cell and T cell immunity were checked for the peptides. For E6 protein, the peptide sequence from 48 to 54 amino acids and one 9-m epitope ETSVHEIEL were the most potential B cell and T cell epitopes, respectively. This peptide could interact with as many as eight MHC-1 alleles and showed high population coverage up to 90.31 %. On the other hand, the peptide region for the E7 protein ranged from 27 to 33 amino acids and two 9-m epitopes QAQPATANY, SSDEDEIGL were found as the most potential B cell and T cell epitopes, respectively. The peptide sequences could interact with as many as seven MHC-1 alleles and showed population coverage up to 90.31 %. Furthermore, conservancy analysis was also performed using in silico tools and showed a conservancy of 100 % for all the selected epitopes. In addition to this, the allergenicity of the epitopes was also evaluated. Although the study requires further in vitro and in vivo screening, this epitope-focused peptide vaccine designing opens up a new skyline that holds a prospective future in HPV research.

In silico/In vivo analysis of high-risk papillomavirus L1 and L2 conserved sequences for development of cross-subtype prophylactic vaccine

“…Conservancy analysis showed that five regions of HPV16,18 L1 protein (8-22, 95-132, 307-342, 398-425 and 449-473) and four regions of HPV16,18 L2 protein (11-40, 54-76, 96-120 and 278-305) were more conserved among other subtypes and could be analyzed as an immunoinformatics input. In B-cell epitope prediction, L1 [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] , L1 408-421 , L1 404-417 , L2 [22][23][24][25][26][27][28][29][30][31][32][33][34][35] , L2 100-113 , L2 94-107 and L2 57-70 had the highest epitope prediction scores. Unfortunately, a reliable method for prediction of B-cell epitope has not been revealed up to now and the sensitivity and specificity of existing methods were very low (the specificity and sensitivity of this method were 0.57 and 0.58, respectively).…”

“…In L1 protein, L1 [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] (EATVYLPPVPVSKVV-type16), L1 408-421 (PPPGGTLEDTYRFV-type16) and L1 404-417 (NFGVPPPPTTSLVD-type 18) epitopes had the best B cell epitope identification scores. For L2 protein, L2 [22][23][24][25][26][27][28][29][30][31][32][33][34][35] (KQSGTCPPDVVPKV-type18), L2 100-113 (PSDPSIVSLVEETS-type16), L2 94-107 (EPVGPTDPSIVTLI-type18) and L2 [57][58][59][60][61][62][63][64][65][66][67][68][69][70] (GLGIGTGSGTGGRT-type16) epitopes showed the highest epitope identification score between their own protein sequences.…”

Prediction and identification of human leukocyte antigen‑A2‑restricted cytotoxic T lymphocyte epitope peptides from the human papillomavirus 58 E7 protein

“…Sabah confirmed the peptide region for the E7 protein ranged from27 to 33amino acids and a 9-m epitopes, SSDEDEIGL, in HPV58 E7 were the most potential T cell epitope. And the peptide sequences could interact with as many as seven MHC-1 alleles and showed population coverage up to 90.31% (26). The CTL epitope for the HPV E6 and E7 antigens were screened by acid elution or the use of synthetic overlapping peptides.…”

Designing of CD8⁺ and CD8⁺-overlapped CD4⁺ epitope vaccine by targeting late and early proteins of human papillomavirus

“…91 Conserved epitopes provide powerful immunization for prolonged period. Sabah et al 92 found that the single 9mer CTL epitope ETSVHEIEL was conserved (100%) in all E6 proteins of HPV58 isolates. While designing an epitope-based vaccine, the use of conserved epitopes may be helpful to provide broader cross-protection across multiple strains.…”

“…Among the five epitopes of E6 protein, RTEVYQFAF [41][42][43][44][45][46][47][48][49] and YSRIRE-LRY [72][73][74][75][76][77][78][79][80] were predicted to have binding affinity for HLA-A*(32:01, 29:02) and HLA-B*58: 01 MHC class I alleles (Table 1D). Out of 13 MHC-binding E7 peptides (Table 1E), STLSFVCPW [93][94][95][96][97][98][99][100][101] (HLA-A*32:01, HLA-B*58:01, HLA-B*57:01), LQQLFLSTL [87][88][89][90][91][92][93][94][95] (HLA-A*02:06), and QLFLSTLSF [89][90][91][92][93][94][95][96][97] (HLA-B*15:02, HLA-B*15:01, HLA-A*32:01) were predicted to have a binding affinity of IC 50 <200 nm. Furthermore, three out of seven epitopes of L1 protein, such as HVEEYDLQF…”