A Comprehensive in Silico Analysis for Identification of Immunotherapeutic Epitopes of HPV-18

Abstract

Human papillomavirus (HPV) remains the major cause of cervical cancer, globally. High risk HPV (Hr-HPV) 16 and 18 together account for more than 70% of cervical cancer cases, whereas the hr-HPV-18 is the second most prevalent hr-HPV type, causing about 5.2% of all cancers worldwide. Considering the high prevalence and mortality rate, cervical cancer remains a noteworthy health problem among women. As of now, no registered immunotherapies are available after the HPV infection. Thus, developing an immunotherapeutic candidate against hr-HPV would be of major clinical benefit. Nowadays, the T-and B-cell peptide based targeted vaccines have been considered as the best candidate for vaccine development against viral infections. In this study, both prophylactic and therapeutic vaccine candidates against hr-HPV-18 were predicted. To achieve this, the prediction of T-and B-cell epitopes of major histocompatibility complex (MHC) were accomplished, that can be used for HPV immunotherapy. For MHC-I, a maximum number (20) of potent peptides were found, against HLA-B*51:01 (L1 = 9, L2 = 6, E2 = 4, and E4 = 1) having percentile value < 1 and, immunogenicity scores higher than 0.5, followed by HLA-A*11:01 (L1 = 8, E2 = 7 L2 = 2, and E6 = 1, E7 = 1); 19 epitopes. For MHC-II, the highest number of peptides found, against the HLA-DRB1*04:01 (L2 = 10, E5 = 7, and E4 = 4), HLA-DRB1*04:05 (E5 = 7, E2 = 5, E4 = 5, and L1 = 4) HLA-DPA1*01:03/DPB1*04:01 (E7 = 7, E6 = 5, L2 = 5, and E2 = 2), HLA-DRB5*01:01(E6 = 6, L1 = 6, and L2 = 6); peptides 21, 21, 19 and 18 respectively. For B-cell, total 94, 16 amino acid long B-cell epitopes were predicted. In conclusion, these predicted epitopes can be valuable candidates for in vitro or in vivo therapeutic vaccine studies against hr-HPV-18 associated cancer.