Application of Liposomes in Antigen Presentation and Cytokine Delivery

Abstract

Introduction

Ever since the liposome has been proposed as an antigen carrier or vaccine adjuvant to enhance immune responses of various vaccines (1), a great deal of effort has been made to understand the physical and chemical properties of the liposome membranes that modulate the potency of liposomal adjuvants [for review, see (2)]. While no generally consistent conclusion can be drawn for all vaccine antigens, the role of lipid fluidity in liposome adjuvanticity has been investigated extensively. Kinsky (3) showed that trinitrophenyl (TNP)-sensitized liposomes composed primarily of gelphased lipids [defined by a gel-to-liquid phase-transition temperature (Tc) higher than 37°C] were more potent in eliciting B cell response. In this study, TNP is a lipid membrane-bound antigen. However, membrane fluidity does not appear to play a role in adjuvanticity with a water-soluble antigen. Six et al. (4) showed, using the water-soluble adenovirus type 5 hexon, that liposomes made of gel-phased lipids – distearoyl phosphatidylcholines (PC) (Tc = 57°C) and dipalmitoyl PC (Tc = 41 °C) - produced similar adjuvant effects in responders compared to liposomes made of liquid-phased lipids – dimyristoyl PC (Tc = 23°C) and dioleoyl PC (Tc = -22°C). Other experimental results regarding membrane fluidity and the adjuvanticity of various lipid compositions and protein antigens (5-8) yielded conflicting conclusions. These inconsistent results may have arisen from the differences in the studied protein antigen and from the unique interaction between the antigen and lipid membrane. Overall, liposome adjuvant studies to date have concentrated on the role of the physical characteristics of liposome membranes in potentiating immune interactions and paid limited attention to the physiological constraint and immune recognition and interaction at the cellular and molecular levels. With the recent advances in our understanding of the cellular and molecular mechanisms of immune regulation, one can now rationally design strategies to deliver antigen and cytokines to selective sites or cells involved in immune potentiation. In the following sections, we will present our observations about such strategies for the delivery of antigens with antigen-presenting liposomes (APLs) targeted to macrophages and the use of liposomes to deliver cytokines for the enhancement of antigen-dependent T and B cell growth.