Pre-clinical Immunogenicity and Anti-tumour Efficacy of a Deleted Recombinant Human Papillomavirus Type 16 E7 Protein

Abstract

Background: Current vaccination strategies against Human papillomavirus (HPV)-induced ano-genital cancers mostly target E7 from HPV16. However, the oncogenic nature of E7 raises potential human safety issues. Although the modifications abrogating the E7 transforming potential have been well characterized, their effect on E7 immunogenicity has been poorly studied. In this study, we evaluated the vaccine potential of an HPV16 E7 protein deleted from the entire pRb-binding motif. Materials and Methods: Purified recombinant deleted (E7Δ21-26) and wild-type (His₆-E7 and E7WT) E7 proteins were studied in pre-clinical mice models. Results: In C57BL/6 mice, E7Δ21-26 formulated with the Quil A adjuvant generated systemic E7-specific cytotoxic T-cell and antibody responses similar to those induced following His₆-E7/Quil A and E7WT/Quil A vaccinations. E7Δ21-26/Quil A injections efficiently protected animals from challenge with the HPV16-expressing tumours, C3 and TC-1. Moreover, therapeutic vaccination with adjuvant-modified E7 suppressed or significantly decreased C3 tumour outgrowth. Conclusion: E7Δ21-26 could represent a safe and efficient vaccine candidate against E7-containing tumour cells.