One of the deadliest malignant cancer in women globally
is cervical
cancer. Specifically, cervical cancer is the second most common type
of cancer in Indonesia. The main infectious agent of cervical cancer
is the human papilloma virus (HPV). Although licensed prophylactic
vaccines are available, cervical cancer cases are on the rise. Therapy
using multiepitope-based vaccines is a very promising therapy for
cervical cancer. This study aimed to develop a multiepitope vaccine
based on the E1 and E2 proteins of HPV 16, 18, 45, and 52 using in
silico. In this study, we develop a novel multiepitope vaccine candidate
using an immunoinformatic approach. We predicted the epitopes of the
cytotoxic T lymphocyte (CTL) and helper T lymphocyte (HTL) and evaluated
their immunogenic properties. Population coverage analysis of qualified
epitopes was conducted to determine the successful use of the vaccine
worldwide. The epitopes were constructed into a multiepitope vaccine
by using AAY linkers between the CTL epitopes and GPGPG linkers between
the HTL epitopes. The tertiary structure of the multiepitope vaccine
was modeled with AlphaFold and was evaluated by Prosa-web. The results
of vaccine construction were analyzed for B-cell epitope prediction,
molecular docking with Toll like receptor-4 (TLR4), and molecular
dynamics simulation. The results of epitope prediction obtained 4
CTL epitopes and 7 HTL epitopes that are eligible for construction
of multiepitope vaccines. Prediction of the physicochemical properties
of multiepitope vaccines obtained good results for recombinant protein
production. The interaction showed that the interaction of the multiepitope
vaccine-TLR4 complex is stable based on the binding free energy value
−106.5 kcal/mol. The results of the immune response simulation
show that multiepitope vaccine candidates could activate the adaptive
and humoral immune systems and generate long-term B-cell memory. According
to these results, the development of a multiepitope vaccine with a
reverse vaccinology approach is a breakthrough to develop potential
cervical cancer therapeutic vaccines.