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

There is a lack of scientific reports on binding cleft interactions of CD8 + epitopes of HPV45 with HLA molecules. Considering this fact, the binding affinity of the potential 27 immunogenic CD4 + epitopes for receptors such as HLA-A*(02:06, 0201, 11:01, 68), HLA-B*(35:01, 58:01), and HLA-C*05:01 was analyzed using docking tools. It is notable that the prophylactic vaccines from HPV L1 protein are used to treat HPV infections in more than 100 countries. 97 In the present study, we found strong binding affinity between the predicted L1 epitope LTAEVMSYI and three different MHC class I alleles HLA-A*(02:06, 02:01, 68, 58:01). Moreover, studies reported that multi-epitope HPV16 E6/E7 vaccine enhanced the clearance of HPVpositive cancer in the mouse model. 98, 99 TA-CIN vaccine was synthesized from a single fusion protein of HPV16 (L2, E6, and E7), and the clinical Phase I study in healthy volunteers showed significant production of IFN-γ which confirmed T-cell immune response in patients. 100 In the present study, minor capsid protein FSDPSIIEV epitope showed affinity for a peptide-binding groove with allele-specific pockets in MHC class I HLA-A*02:01, HLA-A*01:01, HLA-A*68:02, and HLA-C*15:02 alleles. In the case of E6 CD8 + epitopes, RTEVYQFAF showed potential binding interactions with HLA-A*32:01 and HLA-B*58:01 with the highest global binding energy of -61.05 and -58.52 kcal/ mol, respectively. Moreover, E2 is the violent regulator of extra-chromosomal replication and E1 protein expression of the viruses. In addition, the E2 proteins from hrHPV cause apoptosis in HPV-transformed cells compared to E2 from low-risk HPV strains. From the present findings, the E1 epitope FTFPHAFPF exhibited excellent affinity for a peptide-binding groove with allele-specific pockets in MHC class I HLA-A*(32:01, 26:01, 68:02), HLA-B*15:01, and HLA-C*(07:02, 14:02) alleles. The E2 CD8 + epitope CVSYWGVYY exhibited excellent affinity for MHC class I HLA-A*(29:02, 30:02, 11:01, 68:01) alleles.