Antigen–Specific, IgE–Selective Unresponsiveness Induced by Antigen–Liposome Conjugates

Abstract

Background: We have previously reported that ovalbumin (OVA) coupled with liposome via glutaraldehyde (GA) induced OVA–specific– and IgE–selective unresponsiveness in mice. Methods: In this study, OVA–liposome conjugates were made using four different coupling protocols: via GA, N–(6–maleimidocaproyloxy) succinimide (EMCS), disuccinimidyl suberate (DSS) and N–succimidyl–3(2–pyridyldithio)propionate (SPDP) and the induction of antigen–specific IgG and IgE antibody production was investigated for each. In addition, antigen–specific cytokine production by spleen cells of mice immunized either with OVA–liposome or with OVA adsorbed with aluminum hydroxide was investigated. Results: OVA–liposome conjugates coupled via GA or DSS did not induce anti–OVA IgE antibody production but induced substantial anti–OVA IgG antibody production. On the other hand, the induction of anti–OVA IgE unresponsiveness by OVA–liposome conjugates coupled via EMCS or SPDP was incomplete. The amount of interleukin 4 (IL–4) produced by spleen cells stimulated in vitro with OVA correlated well with anti–OVA IgE antibody production in donor mice. However, the production of no other cytokine, i.e., IL–2, IL–5, IL–10 or interferon–γ, was correlated with in vivo IgE antibody production. Conclusion: OVA–liposome coupled via GA or DSS induced complete suppression of anti–OVA IgE production. The results in this study further suggest that the regulation of IgE antibody production does not neccessarily correlate with so–called Th1 cytokine production.

Clinical Application of Surface-Linked Liposomal Antigens

“…We previously reported that surface-linked liposomal antigens induced IgEselective unresponsiveness [10]. The results were consistent even when different procedures for coupling antigens with liposomes [11], or for producing liposomes with different lipid components [12], were employed. During the course of an investigation intended to clarify the mechanism of IgEselective unresponsiveness induced by surface-coupled liposomal antigens, we discovered an alternative approach to regulating the production of IgE, one that is independent of the activity of T cells [13].…”

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

“…Coupling procedure of antigens with liposomes was further investigated (15). OVA-liposome conjugates were generated using four different coupling protocols: GA (Fig.…”

An Increased Adjuvanticity of Liposomes by the Inclusion of Phosphatidylserine in Immunization with Surface-Coupled Liposomal Antigen

“…This phenomenon was consistently observed regardless of the particular antigen coupled to the liposomes [24, 25], the lipid components of the liposomes [26], or the procedure for coupling the antigen and the liposome [27]. Antigen-specific, IgE-selective unresponsiveness was induced by antigen-liposome conjugates only when antigen and liposomes were chemically coupled [28].…”