Liposomes with Differential Lipid Components Exert Differential Adjuvanticity in Antigen−Liposome Conjugates via Differential Recognition by Macrophages

Abstract

We previously reported that liposomes having differential lipid components displayed differential adjuvant effects when antigen was coupled with liposomes via glutaraldehyde. In the present study, antigen-liposome conjugates prepared using liposomes having differential lipid components were added to the macrophage culture, and phagocytosis and the antigen digest of liposome-coupled antigen by macrophages were then investigated. Antigen presentation by macrophages to an antigen-specific T-cell clone was further investigated using the same conjugates. Antigen-liposome conjugates which induced higher levels of antibody production in vivo were recognized more often, and the liposome-coupled antigen was digested to a greater degree by macrophages than antigen-liposome conjugates which induced lower levels of antibody production. These results correlated closely with those regarding antigen presentation by macrophages; when antigen was coupled to liposomes showing higher adjuvant effect, macrophages cocultured with antigen-liposome conjugates activated antigen-specific T-cells at a higher degree. The concentration of OVA in the macrophage culture added as antigen-liposome conjugates was approximately 32 microg/mL. However, the extent of T-cell activation was almost equal to that when 800 microg/mL of soluble OVA was added to the culture. The results of the present study demonstrated that the adjuvant activity of liposomes observed primary in vivo correlated closely with the recognition of antigen-liposome conjugates and antigen presentation of liposome-coupled antigen by macrophages, suggesting that the adjuvant effects of liposomes are exerted at the beginning of the immune response, i.e., recognition of antigen by antigen-presenting cells.

Antigen Chemically Coupled to the Surface of Liposomes Are Cross-Presented to CD8+ T Cells and Induce Potent Antitumor Immunity

“…In fact, surface-linked liposomal Ags induced a significantly higher level of Ag-specific IgG production than that by liposome-encapsulated Ags in mice (our unpublished observation). In addition, a significant difference, which correlated closely with the adjuvant activity of liposomes, was observed in the recognition of liposomal Ags by APCs between liposomes with different lipid components; more Ags coupled to the unsaturated liposomes were engulfed by macrophages in vitro and a higher level of Ag-specific Ab production was induced in vivo than when saturated liposomes were used, suggesting that the adjuvant effects of liposomes are exerted at the beginning of the immune response, i.e., recognition of Ag by APCs (43). In addition to this quantitative difference between liposomes with differential lipid components, in the present study, a qualitative difference (i.e., the differential ability to induce cross-presentation) was observed between saturated and unsaturated liposomes.…”

Application of Surface-Linked Liposomal Antigens to the Development of Vaccines That Induce Both Humoral and Cellular Immunity

“…Liposomes with different lipid components were found to exhibit different adjuvant effects when antigens were chemically coupled to their surfaces (17). The presentation of liposome-coupled OVA was further investigated in vitro, and it was found that OVA coupled to liposomes comprising unsaturated fatty acid was presented to both CD4 ＋ and CD8 ＋ T cells, whereas OVA coupled to liposomes made using saturated fatty acid was presented only to CD4 ＋ T cells.…”

“…To further examine whether the differential adjuvant effects displayed among liposomes with different lipid components were due to the differential recognition of liposomal antigens by APCs, antigen-liposome conjugates prepared using liposomes with differential lipid components were added to macrophage cultures and recognition and digestion of liposomal antigens were compared (17). The antigen-liposome conjugates that induced higher levels of antibody production in vivo were recognized more often by macrophages (Fig.…”

Effect of Liposomal Formulations and Immunostimulating Peptidoglycan Monomer (PGM) on the Immune Reaction to Ovalbumin in Mice

“…The immunoadjuvant activity of liposomes has been established in a large number of studies (Gregoriadis, 1990;Gregoriadis et al, 2000;Tanaka et al, 2004;Kim et al, 2000;Aramaki et al, 1995;de Haan et al, 1995;Alving et al, 1995;Antimisiaris et al, 1993). Liposomes containing both antigen and adjuvant have been proposed as carriers for vaccines (Alving, 1991).…”