Immunoinformatics Approach for Designing an HPV Epitope-Based Vaccine Candidate Harboring Built-in Adjuvants

Cervical cancer is one of main causes of cancer death in women, especially in   developing countries. Therefore, a low-cost broad-spectrum preventive vaccine is immediately needed. The RG-1 epitope of L2 protein is a major cross-neutralizing epitope but has low immunogenicity. This defect can be overcome by using built-in adjuvants such as TLR agonists and bacterial toxoid epitopes. To address this issue, we designed an epitope-based vaccine against HPV16 using immunoinformatic tools.

  The HPV16 RG-1 epitope was linked to built-in adjuvants including the D1 domain of flagellin and RS09 epitope as TLR agonists, and a tetanus toxoid epitope for induction of immune responses. Using immunoinformatic tools, the immunological characteristics of the construct were evaluated. In the first step, MHC-I and II binding, CD4+ T cell immunogenicity prediction, and in the second step, immunogenicity simulation of the construct were investigated.

MHC-I and II predicted epitopes showed a high potentiality to bind to mice and human MHC alleles. The results of the binding of the RG-1 epitope to MHC-I and MHC-II showed that RG-1 could induce humoral and cellular immune response while fused to three built-in adjuvants. Also, the CD4+ immunogenicity assessment results predicted that several epitopes in the designed construct, including epitopes of D1 domain and tetanus toxoid P2 epitope, behaved as potentially strong Th inducers. The immunogenicity simulation results showed that the construct could potentially provide sufficient antigen, and induce suitable humoral and cellular immune responses.

The development of new vaccine strategies has been the focus of several studies. The results showed that the designed construct can potentially provide an effective model for developing a preventive vaccine candidate against a variety of HPV genotypes.