TY - JOUR
T1 - Designing of CD8 + and CD8 + -overlapped CD4 + epitope vaccine by targeting late and early proteins of human papillomavirus
AU - Kaliamurthi, Satyavani
AU - Selvaraj, Gurudeeban
AU - Kaushik, Aman Chandra
AU - Gu, Ke Ren
AU - Wei, Dong Qing
N1 - Funding Information:
The authors are grateful for The Key Research Area Grant 2016YFA0501703 from the Ministry of Science and Technology of China, Henan Natural Science Grant 162300410060, grants from the State Key Lab on Microbial Metabolism, and Joint Research Funds for Medical and Engineering & Scientific Research at Shanghai Jiao Tong University awarded to D-QW. The authors GS and SK are grateful for the Postdoctoral Research Grants 21450003 and 21450004 from Henan University of Technology, Henan Province, China. KG was supported by the research grant 2013BAB11B02 from the Ministry of Science and Technology of China.
Publisher Copyright:
© 2018 Kaliamurthi et al.
PY - 2018/1/1
Y1 - 2018/1/1
N2 - 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.
AB - 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.
KW - Human leukocyte antigen
KW - Killer cells
KW - Overlapped epitopes
KW - Time course simulation
UR - http://www.scopus.com/inward/record.url?scp=85060614187&partnerID=8YFLogxK
U2 - 10.2147/BTT.S177901
DO - 10.2147/BTT.S177901
M3 - Article
AN - SCOPUS:85060614187
SN - 1177-5475
VL - 12
SP - 107
EP - 125
JO - Biologics: Targets and Therapy
JF - Biologics: Targets and Therapy
ER -