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

Persistent 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. In this study, we introduced a lipid nanoparticle encapsulated mRNA vaccine expressing tHA-mE7-mE6, which composed of tHA-the ligand of CD209 on antigen presenting cells (APCs)-and mutated non-tumourigenic mE7 and mE6. This design allowed efficient uptake of antigen by APCs, and the tHA-mE7-mE6 vaccine design has improved immunogenicity compared to conventional antigens (mE7-mE6). In mouse syngeneic tumour model, we confirmed that the vaccine induced strong anti-tumour T-cell immunity in circulation and tumour, Increased the infiltration of immune cells in the tumour, and had outstanding therapeutic and prophylactic efficacy on tumour. The image was created with . image