Immunization with a soluble recombinant HIV protein entrapped in biodegradable microparticles induces HIV-specific CD8 + cytotoxic T lymphocytes and CD4 + Th1 cells

Abstract

One of the major obstacles to the development of successful recombinant vaccines against human immunodeficiency virus (HIV) and other intracellular pathogens is the identification of a safe and effective vaccine delivery system for the induction of cell mediated immunity with soluble protein antigens. In this study it was demonstrated that immunization with a recombinant HIV envelope (env) protein entrapped in biodegradable poly(lactide-co-glycolide) (PLG) microparticles induced consistent HIV-specific CD4 + and CD8 + T-cell responses in mice. Major histocompatibility complex (MHC) class I-restricted cytotoxic T lymphocytes (CTL) responses were detected following a single systemic immunization with gp120 entrapped microparticles and when given by the intranasal (i.n.) route induced HIV-specific CD8 + CTL and secretory IgA. Furthermore immunization with gp120 entrapped in microparticles generated CD4 + T cells that secreted moderate to high levels of IFN-γ. Therefore, PLG microparticles are a safe and effective means of delivering antigen to the appropriate processing site for the generation of class I-restricted CTL, and are also capable of inducing Th1 cells.