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

• Published in: Biologics 2018-01, Vol.12, p.107-125
• Main Authors: Kaliamurthi, Satyavani, Selvaraj, Gurudeeban, Kaushik, Aman Chandra, Gu, Ke-Ren, Wei, Dong-Qing
• Format: Article
• Language: English
• Subjects: Amino acids; Antigens; Cell cycle; Cervical cancer; Efficiency; Epitopes; Genomes; human leukocyte antigen; Human papillomavirus; Immune system; Killer cells; Life sciences; Lymphocytes; Original Research; overlapped epitopes; Peptides; Proteins; time course simulation; Vaccine development; Vaccines
• ISSN: 1177-5475; 1177-5491; 1177-5491
• DOI: 10.2147/BTT.S177901

Human papillomavirus (HPV) is an oncogenic agent that causes over 90% of cases of cervical cancer in the world. Currently available prophylactic vaccines are type specific and have less therapeutic efficiency. Therefore, we aimed to predict the potential species-specific and therapeutic epitopes from the protein sequences of HPV45 by using different immunoinformatics tools. Initially, we determined the antigenic potential of late (L1 and L2) and early (E1, E2, E4, E5, E6, and E7) proteins. Then, major histocompatibility complex class I-restricted CD8 T-cell epitopes were selected based on their immunogenicity. In addition, epitope conservancy, population coverage (PC), and target receptor-binding affinity of the immunogenic epitopes were determined. Moreover, we predicted the possible CD8 , nested interferon gamma (IFN-γ)-producing CD4 , and linear B-cell epitopes. Further, antigenicity, allergenicity, immunogenicity, and system biology-based virtual pathway associated with cervical cancer were predicted to confirm the therapeutic efficiency of overlapped epitopes. Twenty-seven immunogenic epitopes were found to exhibit cross-protection (≥55%) against the 15 high-risk HPV strains (16, 18, 31, 33, 35, 39, 51, 52, 56, 58, 59, 68, 69, 73, and 82). The highest PC was observed in Europe (96.30%), North America (93.98%), West Indies (90.34%), North Africa (90.14%), and East Asia (89.47%). Binding affinities of 79 docked complexes observed as global energy ranged from -10.80 to -86.71 kcal/mol. In addition, CD8 epitope-overlapped segments in CD4 and B-cell epitopes demonstrated that immunogenicity and IFN-γ-producing efficiency ranged from 0.0483 to 0.5941 and 0.046 to 18, respectively. Further, time core simulation revealed the overlapped epitopes involved in pRb, p53, COX-2, NF-X1, and HPV45 infection signaling pathways. Even though the results of this study need to be confirmed by further experimental peptide sensitization studies, the findings on immunogenic and IFN-γ-producing CD8 and overlapped epitopes provide new insights into HPV vaccine development.