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

• Main Authors: Kaliamurthi S, Selvaraj G, Kaushik AC, Gu KR, Wei DQ
• Format: Article
• Language: English
• Published: Dove Medical Press 2018-10-01
• Series: Biologics : Targets & Therapy
• Subjects: human leukocyte antigen; Killer cells; overlapped epitopes; time course simulation
• Online Access: https://www.dovepress.com/designing-of-cd8-and-cd8-overlapped-cd4-epitope-vaccine-by-targeting-l-peer-reviewed-article-BTT

Satyavani Kaliamurthi,1 Gurudeeban Selvaraj,1 Aman Chandra Kaushik,2 Ke-Ren Gu,1,3 Dong-Qing Wei1,2 1Centre of Interdisciplinary Science – Computational Life Sciences, College of Food Science and Engineering, Henan University of Technology, Zhengzhou, China; 2The State Key Laboratory of Microbial Metabolism, College of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China; 3College of Chemistry, Chemical Engineering and Environment, Henan University of Technology, Zhengzhou, China Background and aim: 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.Methods: 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.Results: 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.Conclusion: 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. Keywords: human leukocyte antigen, killer cells, overlapped epitopes, time course simulation