Induction of Innate and Adaptive Immunity with Polyion Complex Nanoparticle Adjuvant Carrying Human Immunodeficiency Virus Type-1 gp120

The development of safe and effective vaccines against human immunodeficiency virus type 1 (HIV-1) infection is mandatory to suppress the global AIDS pandemic. We have recently created polyion complex (PIC) nanoparticles (NPs) using the anionic polymer poly(γ-glutamic acid) (γ-PGA) and the cationic protein protamine. Both materials are biodegradable. HIV-1 gp120-carrying PIC NPs (gp120-PIC NPs) were prepared by mixing γ-PGA-graft-L-phenylalanine ethylester polymer with protamine containing gp120 antigen in phosphate-buffered saline, and their effect on the induction of innate and adaptive immune responses was examined in mice. gp120-PIC NPs were efficiently taken up into dendritic cells (DCs). PIC NPs upregulated surface costimulatory molecule expression and cytokine production through the mitogen-activated protein kinase-mediated nuclear factor κB signaling pathway in DCs. The immunization of mice with gp120-PIC NPs resulted in robust induction of antigen-specific CD8⁺ T cells as well as IgG antibodies. In contrast, such induction was not observed, when mice were immunized with gp120 alone or gp120 plus Alum-base adjuvant or incomplete Freund's adjuvant. Furthermore, PIC NPs could induce antigen-specific effector and central memory CD8⁺ T cells. These results suggest that PIC NPs have potential as an effective vaccine adjuvant against various infectious diseases including HIV-1/AIDS.