Background: Human Papillomavirus (HPV) is responsible for substantial morbidity and
mortality worldwide. We predicted immunogenic promiscuous monovalent and polyvalent T-cell
epitopes from the polyprotein of the Human Papillomavirus (HPV) using a range of bioinformatics
tools and servers.
Methods: We used immunoinformatics and reverse vaccinology-based approaches to design prophylactic
peptides by antigenicity analysis, T-cell epitopes prediction, proteasomal and conservancy
evaluation, host-pathogen protein interactions, and in silico binding affinity analysis.
Results: We found two early proteins (E2 and E6) and two late proteins (L1 and L2) of HPV as potential
vaccine candidates. Of these proteins (E2, E6, L1 & L2), 2-epitopes of each candidate protein
for multiple alleles of MHC class I and II were found, bearing significant binding affinity
(>-6.0 kcal/mole). These potential epitopes for CD4+ and CD8+ T-cells were also linked to design
polyvalent construct using GPGPG linkers. Cholera toxin B and mycobacterial heparin-binding hemagglutinin
adjuvant with a molecular weight of 12.5 and 18.5 kDa were used for epitopes of
CD4+ and CD8+ T-cells, respectively. The molecular docking indicated the optimum binding
affinity of HPV peptides with MHC molecules. This interaction showed that our predicted vaccine
candidates are suitable to trigger the host immune system to prevent HPV infections.
Conclusion: The predicted conserved T-cell epitopes would contribute to the imminent design of
HPV vaccine candidates, which will be able to induce a broad range of immune-responses in a
heterogeneous HLA population.