Designing a therapeutic and prophylactic candidate vaccine against human papillomavirus through vaccinomics...

Human papillomavirus (HPV) is the main cause of cervical cancer, the 4^th prominent cause of death in women globally. Previous vaccine development projects have led to several approved prophylactic vaccines available commercially, all of which are made using major capsid-based (L1). Administration of minor capsid protein (L2) gave rise to the second generation investigational prophylactic HPV vaccines, none of which are approved yet due to low immunogenicity provided by the L2 capsid protein. On the other hand, post-translation proteins, E6 and E7, have been utilized to develop experimental therapeutic vaccines. Here, in silico designing of a therapeutic and prophylactic vaccine against HPV16 is performed.

In this study, several immunoinformatic and computational tools were administered to identify and design a vaccine construct with dual prophylactic and therapeutic applications consisting of several epitope regions on L2, E6, and E7 proteins of HPV16.

Immunodominant epitope regions (aa 12-23 and 78-78 of L2 protein, aa 11-27 of E6 protein, and aa 70-89 of E7 protein) were employed, which offered adequate immunogenicity to induce immune responses. Resuscitation-promoting factors (RpfB and RpfE) of Mycobacterium tuberculosis were integrated in two separate constructs as TLR4 agonists to act as vaccine adjuvants. Following physiochemical and structural evaluations carried out by various bioinformatics tools, the designed constructs were modeled and validated, resulting in two 3D structures. Molecular docking and molecular dynamic simulations suggested stable ligand-receptor interactions between the designed construct and TLR4.

Ultimately, this study led to suggest the designed construct as a potential vaccine candidate with both prophylactic and therapeutic applications against HPV by promoting Th1, Th2, CTL, and B cell immune responses, which should be further confirmed in experimental studies.