Enhanced mucosal and systemic immunogenicity of human papillomavirus-like particles encapsidating interleukin-2 gene adjuvant

Here, we report the enhanced mucosal and systemic immunogenicity of human papillomavirus type (HPV) 16 L1 virus-like particles (VLP) encapsidating a cytokine genetic adjuvant. Plasmid DNA expressing interleukin-2 (pIL2) was encapsidated in VLP using the reassembly property of VLP from disassembled L1 capsomeres. pIL2 in reassembled VLP showed stability against DNase I, indicating encapsidation. After intramuscular immunization into mice, the highest vaginal and salivary HPV16 L1-specific IgA titers were observed in pIL2-encapsidated VLP, followed by VLP plus pIL2 in separate plasmid, and VLP alone. Similar to mucosal responses, serum IgG, IgG ₁, and IgG _2a antibody titers were the highest in the group treated with pIL2-encapsidated VLP. Moreover, the adjuvanticity of pIL2 encapsidated in VLP was stronger in IgG _2a antibody relative to IgG ₁ antibody. Our results indicate that the encapsidation of a genetic cytokine adjuvant pIL2 would be beneficial for more effective induction of mucosal and systemic immune responses to VLP vaccines.