Induction of Potent CD8 + T-Cell Responses by Novel Biodegradable Nanoparticles Carrying Human Immunodeficiency Virus Type 1 gp120

Abstract

ABSTRACT The mainstream of recent anti-AIDS vaccines is a prime/boost approach with multiple doses of the target DNA of human immunodeficiency virus type 1 (HIV-1) and recombinant viral vectors. In this study, we have attempted to construct an efficient protein-based vaccine using biodegradable poly(γ-glutamic acid) (γ-PGA) nanoparticles (NPs), which are capable of inducing potent cellular immunity. A significant expansion of CD8 + T cells specific to the major histocompatibility complex class I-restricted gp120 epitope was observed in mice intranasally immunized once with gp120-carrying NPs but not with gp120 alone or gp120 together with the B-subunit of cholera toxin. Both the gp120-encapsulating and -immobilizing forms of NPs could induce antigen-specific spleen CD8 + T cells having a functional profile of cytotoxic T lymphocytes. Long-lived memory CD8 + T cells could also be elicited. Although a substantial decay in the effector memory T cells was observed over time in the immunized mice, the central memory T cells remained relatively constant from day 30 to day 238 after immunization. Furthermore, the memory CD8 + T cells rapidly expanded with boosting with the same immunogen. In addition, γ-PGA NPs were found to be a much stronger inducer of antigen-specific CD8 + T-cell responses than nonbiodegradable polystyrene NPs. Thus, γ-PGA NPs carrying various HIV-1 antigens may have great potential as a novel priming and/or boosting tool in current vaccination regimens for the induction of cellular immune responses.