Heterologous Prime-boost Vaccination Using Adenovirus and Albumin Nanoparticles as Carriers for Human Papillomavirus 16 E7 Epitope

Abstract

Background: Nanocarriers are these days considered an attractive approach in cancer immunotherapy owing to their ability to deliver antigens to antigen-presenting cells (APCs) for stimulating robust immune cells against the tumor. Objectives: The objective of this study was to construct nanocomplexes using two nanocarriers with negative surface charge, adenovirus (Ad) and human serum albumin nanoparticle (HSA-NP), and coat their surface with a modified and positively-charged HPV16 E7 MHC-I specific epitope to assess their anti-tumor effects in a TC-1 mouse model. Methods: After the construction of Ad and HSA-NP, their complexes with HPV16 E7 MHC-I specific epitope were characterized by zeta potential and dynamic light scattering. Then, the cellular immunity and CTL responses in immunized mice were assessed by measuring the levels of IL-10 and IFN-γ and the expression of CD107a, a marker of CTL response, as well as tumor inhibition. Results: The zeta potential and dynamic light scattering results showed that incubation of the oppositely- charged nanocarriers and MHC-I specific epitope led to the formation of nanocomplexes in which the surface charge of nanocarriers was changed from negative to positive with minimal changes in the particle size. We demonstrated that the nanocomplex platforms in heterologous primeboost regimens generate significantly higher E7-specific IL-10, IFN-γ, and CTL responses. Moreover, the heterologous nanocomplex regimens, Alb/Pep-Ad/Pep and Ad/Pep-Alb/Pep, significantly suppressed the growth of TC-1 tumors in vivo compared with mice receiving homologous regimens and naked nanocarriers. Conclusion: The heterologous nanocomplexes might serve as an effective vaccine strategy against HPV-induced cervical cancer.