Immunoinformatics-Driven Design of an HPV-16 and -18 Synthetic Long Peptide Vaccine

Background and Aim: Human papillomavirus types 16 and 18 cause most cervical cancers worldwide. Existing VLP-based vaccines are unable to eliminate ongoing highly oncogenic infections. This study suggests an SLP-based vaccine for already infected patients, even with precancerous lesions. Methods: HPV16/18 E6 and E7 proteins' potent HLA class I and class II-restricted epitopes were extracted from IEDB or predicted by ANNs (IC50 90% of the residues in the most favorable regions reflect good quality 3D structures. Molecular docking studies provided a ΔG of −13.20±1.42 kcal/mol, and an average Kd of 3.5×10−9 M. MD simulations reflect favorable thermodynamic properties, based on mild RMSD ([0.1;0.87] nm), RMSF, SASA (49.37±1.54 nm2) and Rgyr ([1.15;1.34]) fluctuations over the 100-ns simulations. Conclusions: 25 in silico-designed SLPs stimulate both innate and adaptive immunity, with little to no toxic or allergenic effects. The presented vaccination platform could exert both a therapeutic (by tumor cell clearance) and a prophylactic effect (by eradicating E6 and E7+ premalignant cells)