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

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

MHC class I-presenting peptides are synthesized from endogenous processing pathway-derived proteins. 85 We predicted 50 potential CD8 + MHC class I-restricted 9mer epitopes based on endogenous processing pathway (proteasomal cleavage, TAP transport, and MHC class I binding algorithm) by using combined methods in the IEDB. The α-chain of MHC class I contains the peptidebinding domain, immunoglobulin-like domain, and a transmembrane region. The heavy chain of the MHC class I molecule is coded by the genes at HLA (A, B, and C) loci. The MHC genes are highly polymorphic in nature; it means the residues in the N-and C-terminal regions of MHC proteins could generate clefts for specific peptide binding. MHC class I alleles exhibit broader binding specificity for peptides between 1,000 and 10,000 amino acids with high promiscuity. 86 Neural networks based on computational approaches have played a vital role in the prediction of the binding affinity of a peptide for specific MHC molecules. 87 In the present study, the FTFPHAFPF, CVSYWGVYY, LTAEVMSYI, and FSDPSIIEV antigenic epitopes were found to interact with more number of HLA alleles. This specific high-binding affinity is absolutely desired because the efficiency of an epitope in vaccine development greatly depends on the extent of its interaction with HLA alleles. Moreover, activated CD8 + cells kill the targets through three crucial mechanisms including secretion of antitumor and antiviral (IFN-γ) substances, 88 membrane disruption by granulysin, and Fas-mediated killing. 89 Recent studies reported the prevalence rate of multiple hrHPV genotypes in cervical cancer 90 and the poor survival rate associated with invasive cervical carcinomas. Moreover, the hrHPV strains co-infection has been shown to increase the death rate of HIV patients. 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. The present study demonstrated that 14 immunogenic CD8 + epitopes showed cross-protection against more than 12 hrHPVs.