Design of a multiepitope vaccine from the HPV E1 and E2 proteins with an immunoinformatics and molecular dynamics approach
Rizarullah (a), Reza Aditama (a), Ernawati Arifin Giri-Rachman (b), Rukman Hertadi (a*)

a) Biochemistry Research Division, Faculty of Mathematics and Natural Sciences, Bandung Institute of Technology, Jl. Ganesa No. 10, Bandung 40132, Indonesia
b) Genetics and Molecular Biotechnology Research Division, School of Life Sciences and Technology, Bandung Institute of Technology, Jl. Ganesa No. 10, Bandung 40132, Indonesia

Abstract

Cervical cancer caused by human papillomavirus (HPV) is the fourth leading cause of death among women. Several commercial prophylactic vaccines are used to prevent HPV infection. However, these prophylactic vaccines have no therapeutic effect against previous infections of HPV as viral strategies to evade the immune system can increase HPV infection. Thus, this study aimed to develop a multiepitope vaccine based on the target proteins E1 and E2 of HPV 16, 18, 45, and 52 using bioinformatics. In this study, cytotoxic T lymphocyte (CTL) and helper T Lymphocyte (HTL) epitopes were predicted and their allergenicity, toxicity, and antigenicity were evaluated. The epitopes were constructed into a multiepitope vaccine using AAY linkers between the CTL epitopes and GPGPG linkers between the HTL epitopes. The tertiary structure of the multiepitope vaccine was modeled and refined with alphaFold 2.3 and GalaxyRefine, respectively. The quality of the tertiary structure model was evaluated by Ramachandran plots and Prosa-web and revealed that the vaccine construct had a good structural conformation. Molecular docking analysis and dynamic molecular simulation were performed to validate the interaction of the vaccine-TLR4 complex and the stability of the formed interaction, showing that the multiepitope vaccine interacted well with Toll Like Receptor 4 (TLR4). Vaccine-TLR4 binding affinity was calculated using MMGBSA, resulting in a binding value of -143.6992 kcal/mol. These results suggest that the proposed vaccine can be considered effective as a therapeutic vaccine. However, further in vitro and in vivo testing is needed to validate the effectiveness of the vaccine.

Keywords: Cervical cancer- Human papillomavirus- Immunoinformatics- Multiepitope Vaccine- Molecular docking- Molecular dynamic

Topic: Biokimia Komputasi