Beyond prevention: in silico designing a one-two punch novel therapeutic vaccine candidate against major oncoproteins of HPV 16, 18, 31, and 45 and subsequent cervical cancer

The human papillomavirus (HPV) is the most prevalent viral sexually transmitted disease (STD). HPV 16, 18, 31 and 45 are most associated with the development of cervical cancer. Currently approved HPV vaccines are only preventive and have no therapeutic activity. With immunoinformatics approaches, we tried to design a novel vaccine against E6 and E7 oncoproteins of HPV 16, 18, 31 and 45 for the prevention and treatment of cervical cancer. The tertiary structure of the vaccine was modelled and validated. The vaccine was docked with TLR4 and TLR9 receptors, which have an undeniable anti-tumour immunity against cervical cancer. Molecular dynamic simulation indicates that the vaccine-TLR complexes were structurally stable. Immune stimulation and population coverage analysis results were much better than similar studies. Our new multi-epitope vaccine is the first HPV vaccine to target the E6 and E7 antigens of HPV 16, 18, 31 and 45. Also, this is the first study to target conserved regions of HPV and then merge the T and B cell epitopes as a regional epitope, which increases vaccine efficacy and reliability. We hope that the methodology of this study will even shed light on the design of vaccines against other viral STDs.