Immunomodulating Properties of Substances to Be Used in Combination with Liposomes

Abstract

Liposomes haptenated with tripeptide-enlarged dinitrophenyl (DNP) are known to act as thymus-independent antigens which induce a strong IgM response and only limited amounts of circulating IgG. When haptenated liposomes are used in vaccination studies, it is of practical importance to improve the immunogenicity of these complexes. Therefore, an evaluation was made of the potency of various substances to modulate the immune response in such a way that the total antibody production is increased, including a relative great increase of 2-merecaptoethanol (2-ME)-resistant antibodies and immunological memory is induced. The following substances were used: glycophorin A (GP-A), sialogangliosides (monosialo-, disialo- and trisialogan-glioside), 6–0-stearoyl-MDP (MDP-SA) and lipid A (lip A). Lip A incorporated into liposomes was the only substance inducing considerable increases of both total and 2-ME-resistant haemagglutination (HA) titre after immunization. Depending on the dose tested, the sialic-acid-containing protein GP-A had a small and varying influence on the serum antibody response. Sialogangliosides transiently decreased in a dose-dependent manner the total antibody titre in serum. In contrast to lip A, the lipophilic bacterial adjuvant MDP-SA did not influence HA titres significantly. The number of plaque-forming cells (PFC) in the spleen was enhanced considerably after both primary and secondary immunization with liposomes containing lip A. The other substances tested induced only minor differences of the number of PFC. To some extent, lip A induced immunological memory. In conclusion, it can be stated that of the agents tested, only lip A is a potent and consistent stimulator of the humoral immune response to liposomes haptenated with DNP groups. Sialogangliosides induced a transient decrease of the immune response to haptenated liposomes.