Immunoinformatics applications in the development of therapeutic vaccines against human papillomavirus-related infections and cervical cancer.

The human papillomavirus (HPV) represents the most prevalent sexually transmitted infectious agent worldwide. HPV penetrates the epithelium through microlesions and establishes an infectious focus that can lead to the development of cervical cancer. Prophylactic HPV vaccines are available, but do not affect already-established infections. Using in silico prediction tools is a promising strategy for identifying and selecting vaccine candidate T cell epitopes. An advantage of this strategy is that epitopes can be selected according to the degree of conservation within a group of antigenic proteins. This makes achieving comprehensive genotypic coverage possible with a small set of epitopes. Therefore, this paper revises the general characteristics of HPV biology and the current knowledge on developing therapeutic peptide vaccines against HPV-related infections and cervical cancer.

Immunoinformatics-based characterization of immunogenic CD8 T-cell epitopes for a broad-spectrum cell-mediated immunity against high-risk human papillomavirus infection.

Human papillomavirus (HPV) represents the most prevalent sexually transmitted infectious agent worldwide. Vaccination has been an approach successfully used as a prophylactic measure against this infectious agent in patients without previous contact with the genotypes present in the vaccine. In this work, we use a computational approach to predict CD8 T cell epitopes from HPV proteins to promote cell-mediated immunity. We evaluated immunogenicity, conservation, toxicity, stability and population coverage of epitopes. Finally, a molecular docking analysis was performed to confirm the stability of the complexes formed. We identified 17 epitopes with affinity for several HLA alleles, covering 5 binding supermotifs (A2, A3, A24, B62 and B57). The analyses showed that these epitopes have a high population coverage and are highly conserved among several HPV genotypes. Seven of them (NWKNFFSTTWE1594-603, KVSAFQYRVFRVL163-74, LQFIFQLCKL1372-380, RVFRVQLPDPNKL170-81, FNKPYWLHRL1307-315, FITCVDTTRL1330-338 and HLRREQIFARL1248-257) were 100% conserved. Finally, molecular docking confirmed the stability of the complexes by means of a large network of hydrogen bonds formed and the calculated low bonding energy. The epitopes identified in this study are potential candidates as components of therapeutic vaccines and we suggest that these epitopes can be used in future studies aiming to activate antigen-specific CD8 T cells.