Prevention and treatment of HPV‐related cancer through a mRNA vaccine expressing APC‐targeting antigen

Abstract

AbstractPersistent human papillomavirus (HPV) infection is associated with multiple malignancies. Developing therapeutic vaccines to eliminate HPV‐infected and malignant cells holds significant value. In this study, we introduced a lipid nanoparticle encapsulated mRNA vaccine expressing tHA‐mE7‐mE6. Mutations were introduced into E6 and E7 of HPV to eliminate their tumourigenicity. A truncated influenza haemagglutinin protein (tHA), which binds to the CD209 receptor on the surface of dendritic cells (DCs), was fused with mE7‐mE6 in order to allow efficient uptake of antigen by antigen presenting cells. The tHA‐mE7‐mE6 (mRNA) showed higher therapeutic efficacy than mE7‐mE6 (mRNA) in an E6 and E7+ tumour model. The treatment resulted in complete tumour regression and prevented tumour formation. Strong CD8+ T‐cell immune response was induced, contributing to preventing and curing of E6 and E7+ tumour. Antigen‐specific CD8+ T were found in spleens, peripheral blood and in tumours. In addition, the tumour infiltration of DC and NK cells were increased post therapy. In conclusion, this study described a therapeutic mRNA vaccine inducing strong anti‐tumour immunity in peripheral and in tumour microenvironment, holding promising potential to treat HPV‐induced cancer and to prevent cancer recurrence.