Development of multiepitope therapeutic vaccines against the most prevalent high-risk human papillomaviruses

Area of Science:

• * Immunology
• * Vaccinology
• * Oncology

Background:

• * Cervical cancer is a significant global health issue, primarily caused by persistent high-risk human papillomavirus (HPV) infections.
• * Current HPV vaccines are prophylactic and target only a few HPV types, necessitating the development of therapeutic vaccines against existing tumors.

Purpose of the Study:

• * To develop and evaluate DNA- or peptide-based multiepitope vaccines targeting HPV E7, E6, and E5 oncoproteins.
• * To assess the prophylactic and therapeutic anti-tumor effects of these vaccines in a preclinical mouse model.

Main Methods:

• * Bioinformatic tools were used to design multiepitope constructs targeting E7, E6, and E5 oncoproteins from HPV types 16, 18, 31, and 45.
• * Mice were vaccinated using homologous and heterologous prime-boost strategies in prophylactic and therapeutic settings.
• * Anti-tumor efficacy was evaluated by monitoring tumor rejection.

Main Results:

• * Both homologous E7+E6+E5 polypeptide and heterologous E7+E6+E5 DNA prime/polypeptide boost vaccination strategies resulted in complete tumor rejection.
• * These positive outcomes were observed in both prophylactic and therapeutic experimental settings.

Conclusions:

• * The developed multiepitope constructs are effective in inducing anti-tumor immunity against HPV-associated tumors.
• * These findings suggest that the designed multiepitope vaccines hold significant potential as therapeutic agents for HPV-induced cancers.