Heterologous administration of HPV16 E7 epitope-loaded nanocomplexes inhibits tumor growth in mouse model.

The nanostructured complexes can result in enhanced vaccine efficacy by facilitating the distribution and uptake of antigens by antigen-presenting cells (APCs), thereby stimulating immune responses. Here, we hypothesized that either directly coating of nanoadjuvants including aluminum phosphate (AlPO) and adenovirus (Ad) with a modified HPV16 E7 MHC-I specific epitope, RAHYNIVTF, or mixing the CpG oligodeoxynucleotide (CpG-ODN) with the cationic epitope to form nanocomlexes, and their combinational therapy would enhance their anti-tumor effects in a TC-1 mouse model. The positively-charged HPV16 E7 epitope was attracted to the oppositely-charged adjuvants by electrostatic interaction to generate epitope/adjuvant nanocomplexes. We showed that coating the nanosized adjuvants with the cationic epitope increased the particles' surface charge without significant change in their size. We then tested the cellular immunogenicity and therapeutic efficacy of nanocomplexes by measuring IL-10 and IFN-γ production, the expression of CD107a as a marker of CTL response, and tumor growth inhibition. The nanocomplexes were administered either in homologous or heterologous prime-boost regimens, and heterologous immunizations including Ad/Pep-CpG/Pep, CpG/Pep-Ad/Pep, Ad/Pep-Alum/Pep, and Alum/Pep-Ad/Pep induced significantly higher levels of IL-10, IFN-γ, and CD107a-expressing CD8 T cells compared with homologous administrations. Furthermore, the tumor growth was significantly suppressed in mice receiving nanostructured complexes in the heterologous immunizations. Our study highlights the potential of the heterologous prime-boost administration of the epitope-coated nanostructures as an effective immunization strategy.