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

Satyavani Kaliamurthi, Gurudeeban Selvaraj, Aman Chandra Kaushik, Ke Ren Gu, Dong Qing Wei

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


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.

Original languageEnglish
Pages (from-to)107-125
Number of pages19
JournalBiologics: Targets and Therapy
StatePublished - 1 Jan 2018
Externally publishedYes


  • Human leukocyte antigen
  • Killer cells
  • Overlapped epitopes
  • Time course simulation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Oncology
  • Gastroenterology
  • Pharmacology (medical)


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