Integrative bioinformatics approach to the mRNA vaccine development for the human papillomavirus using the capsid protein

Human papillomavirus (HPV) is associated with several serious diseases, consisting of neck-related, lung, oropharyngeal, vaginal, penile, vulvar, and anal tumors. Potential candidates for mRNA vaccination include the capsid structural peptides L1 and L2, which are prominently recognized by the immune system. This recognition has resulted in the formation of mRNA vaccines targeting these capsid proteins. We employed various bioinformatics methods to predict epitopes for helper CD4 + lymphocytes, CD8 + lymphocytes, and B cells within these proteins, and to evaluate their allergenicity, toxicity, and antigenicity. An orthorhombic TIP3P water box with a buffer region of 10 Å was used for the experiment, and Na⁺/Cl⁻ counter-ions at physiological salt concentration (0.15 M) were included to counteract the system. After equilibration of the NVT and NPT ensembles, a 100 ns production run was conducted at 310 K and 1 atm. Our vaccine construct includes 24 epitopes, comprising both CTLs and HTLs. The vaccine exhibited enhanced hydrophilicity, with an average hydropathicity score of -0.811. The Ramachandran plot indicated remarkable stability, with 94.3% of residues located within the allowed and additionally allowed regions. The vaccine demonstrated significant affinity for the TLR3 receptor, as evidenced by a docking score of -363.44 and a confidence score of 0.9862. Following codon optimization, expression in E. coli vectors showed substantial improvement in vaccine production, reflected by an increased GC content of 58.12%. MM-GBSA analysis revealed a consistent binding affinity for TLR3 at -53.16 kcal/mol. Overall, the designed vaccines against HPV capsid proteins represented favorable outcomes through strong immune responses, supporting their progression to in vitro and in vivo clinical trials.