Development of HPV nanovaccine candidate based on IL-15-E7 fusion protein encapsulated in silk-fibroin nanoparticles.

Human papillomavirus type 16 (HPV16) infections account for most cases of cervical cancer that occur throughout the world. The HPV E7 oncoprotein is known as a crucial target antigen for developing a therapeutic HPV vaccine. In this research, we designed a recombinant fusion protein comprising the IL-15 cytokine linked to HPV16 E7. This fusion protein was subsequently encapsulated in silk fibroin nanoparticles (SFNPs). The immune responses and antitumor effects of nanovaccine candidate were assessed in a tumor mouse model. Our data showed that the IL-15-E7 fusion protein-encapsulated SFNPs had a nano-sized structure (77.402 ± 7.852 nm) with a negative charge (-11.1 mV). Furthermore, the nanovaccine formulation induced higher IFN-γ and Granzyme B secretion than the recombinant IL-15-E7 fusion protein in mice. Compared to the recombinant IL-15-E7 fusion protein, the nanovaccine formulation showed a higher survival rate in a mouse tumor challenge (75% vs 50%), and a non-significant substantial tumor growth inhibition. In general, the IL-15-E7 fusion protein-encapsulated SFNPs significantly induced Th1 immunity, CTL activity, and anti-tumor effects, suggesting a promising nanovaccine candidate against HPV infections.