Immunogenicity of Liposomal Model Membranes Sensitized with Dinitrophenylated Phosphatidylethanolamine Derivatives Containing Different Length Spacers

Abstract

The immunogenicity of liposomes sensitized with dinitrophenylated (DNP) phosphatidylethanolamine (PE) derivatives, differing in the length of the spacer linking DNP to PE, has been examined. The magnitude of the anti-DNP response of mice was influenced by the number of methylene and amino groups interposed between DNP and the amino function of PE; generally, derivatives containing very short or long spacers were less effective immunogens than those of intermediate length. The epitope density of the derivative in the lipid bilayers, but not the dose, also affected the relative immunogenicity of the different derivatives. Incorporation of lipid A, which has been previously demonstrated to enhance liposomal immunogenicity, increased the response to those derivatives that elicited antibodies in the absence of this polyclonal B cell mitogen; however, the relative immunogenicity of the derivatives was not significantly altered. A good correlation was observed between the ability to bind low affinity IgG and IgM antibodies in vitro (determined by complement-dependent glucose release from liposomes) and in vivo immunogenicity. These results suggest that the ability of sensitized liposomes to elicit a response requires the extension of the antigenic determinant away from the surface of the lipid bilayer.