Design and computational evaluation of a prophylactic and therapeutic multi-epitope vaccine candidate against...

Cervical cancer is the fourth most common cancer among women worldwide, caused by the human papillomavirus (HPV). HPV16 /18 are strongly associated with the development of cervical cancer. HPV vaccines are not widely available in economically underdeveloped areas. They also have limited efficacy against pre-existing HPV infections and cervical lesions. Therefore, the study aims to computationally design a vaccine that induces both prophylactic and therapeutic immunity against cervical cancer. Using computational approaches, we designed a multi-epitope vaccine incorporating 62 cytotoxic T lymphocyte (CTL) epitopes, 7 helper T lymphocyte (HTL) epitopes, and 3 linear B-cell epitopes from conserved regions of HPV16/18 E6, E7, and L2 proteins. To increase immunogenicity, the adjuvant RS-09 (APPHALS) was added to the N-terminal of the vaccine. The chosen CTL and HTL epitopes have the potential to achieve 100% worldwide population coverage. The vaccine candidate has appropriate physicochemical properties. The vaccine's secondary and tertiary structures were predicted, followed by refinement and validation of the models. The vaccine has a high affinity for Toll-like receptor 4 (TLR4), as indicated by its molecular docking score of -1164.4 kcal/mol and RMSD fluctuation range of 17 to 22.5 angstroms (Å) at the end of the MD simulation period. Immune response simulation showed that the vaccine candidate could induce strong humoral and cellular immune responses. The vaccine sequence's GC content was calculated to be 48.99%, and subsequently, in silico cloning of the vaccine was performed in the pET28a (+) vector. The results reveal that this vaccine is highly immunogenic; however, experimental testing is required to confirm its efficacy and safety.