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

Currently available prophylactic vaccines such as Gardasil (HPV6, 11, 16, and 18) and Gardasil 9 (HPV31, 33, 45, 52, and 58) could provide protection to women by inducing significant immunity, but these vaccines are limited to those aged between 9 and 26 years. 11 However, these prophylactic vaccines demonstrated no therapeutic benefits in patients who already had HPV infections. 12, 13 The US Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDCP) have recommended that HPV vaccines are safe but can cause more pain, uneasiness, soreness, and Guillain-Barre syndrome in patients. 14, 15 However, to control the prevalence rate of high-grade HPV infections, species-specific screening and vaccination will be needed. 16 Out of 150 types of HPV, the 13 high-risk HPV (hrHPV) types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68) which induce uncontrolled cell growth in the cervix uteri region have been identified. 17, 18 Among these, HPV16 and 18 were reported as the major strains to cause cervical cancers (about 67.4%) around the world. [19] [20] [21] In fact, the contributions of other hrHPV types are limited due to their geographical distribution. HPV45 is a member of HPV18 alpha papillomaviridae family and a species of α7. [22] [23] [24] Moreover, the prevalence rate of HPV45 in cases of cervical cancer was found to be high varying from 1.6% to 37.4% which was recorded in different geographical regions such as Ghana, Portugal, Serbia, Spain, Pakistan, USA, Japan, Burkina Faso, Northern parts of China, Southeast regions of Brazil, and Northeast of India. 18, [25] [26] [27] [28] [29] [30] [31] [32] Difference in the host genetic framework and oncogenicity of the circulating variants might play a critical role in geographical distribution of HPV45. Together with HPV16 and 18, HPV45 is highly recorded in cases of squamous cell carcinoma (75%) and adenocarcinoma (94%), and in cases of invasive cervical cancer and cervical intraepithelial neoplasia grade 3. 2, 16, 33 Based on the level of enrichment in cervical cancer cases compared to women with normal cytological features, HPV45 has been suggested as the third highest oncogenic agent next to HPV16 and 18. 1, 30, 34, 35 In comparison to other hrHPV types, limited reports exist about the peptide research in HPV45.