Immunoinformatics Approach to Develop a Novel Chimeric L1/L2 mRNA-based Vaccine against a Broad Spectrum of Human Papillomavirus (HPV) Species

(1) Background: Human papillomaviruses (HPV) are primarily related to cervical cancer around the world. This study presented an in silico design of a chimeric L1/L2 mRNA-based vaccine candidate against a diverse spectrum of human papillomaviruses; (2) Methods: We employed a computational strategy to predict and screen for antigenicity, allergenicity, toxicity, and conservation of immunodominant cytotoxic T cells, helper T cells, and linear B-cell epitopes from the most conserved HPV L1 and L2 proteins. The selected epitope peptides were coupled together with appropriate linkers to create a multi-epitope chimeric peptides. The mRNA-based vaccine was developed by combining an optimized open reading frame with co-translation regulation and co-transcription components; (3) Results: Twenty five (25) non-toxic, non-allergenic, highly antigenic, and conserved epitopes were identified. The final vaccine had a molecular weight of 60161.29 kDa, a theoretical pI of 9.44, and a solubility of 0.451. The mRNA-based vaccine had a stable mRNA structure with a minimum free energy of -731.10 kcal/mol and an estimated molecular weight of 644.98 kDa. The suggested vaccine had no cross-affinity for the human genome and achieved a global population coverage rate of 86.24%. The vaccine demonstrated a stable docking complex and robust interactions with Toll-like receptor 4 (TLR4) with binding affinities of -1377.5 kcal/mol and was capable of stimulating immunoglobulin IgG, IgM, T and B cells lymphocytes, and cytokines by in silico simulation; (4) Conclusion: The vaccine is considered a preventive and therapeutic candidate; however, further in vitro and in vivo tests are needed to prove its safety and efficacy.