Enhanced antibody response to liposome-associated protein antigens: preferential stimulation of IgG2a/b production.

The effect of liposome encapsulation on the antibody response to bovine serum albumin (BSA), human carcinoembryonic antigen (CEA) and sheep IgG (sIgG) has been determined in the mouse. Dipalmitoylphosphatidylcholine/dimyristolylphosphatidylglycerol liposomes (10:1 molar ratio; 1 mumol) containing BSA, CEA or sIgG induced significant levels of IgG antibodies after one injection, and enhanced the proportion of IgG2a/2b to IgG1 on subsequent boost injection. The IgG antibody titre induced by liposomal antigen was 100-400-fold greater than immunization with antigen alone. Immunization with antigen and the water-soluble adjuvant N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP; 50 micrograms) resulted in antibody titres intermediate between free and liposomal antigen. MDP did not enhance the proportion of IgG2a/2b to IgG1. Incorporation of the lipid soluble MDP derivative MDP-glycerol dipalmitate (MDP-GDP; 10 micrograms) liposomes containing protein antigens resulted in higher titres and enhanced IgG2b isotype expression. Analysis of serum IgG antibody-isotype levels after immunization and boost with BSA/MDP showed that the half-life of IgG2a/2b and IgG3 was significantly less than that of IgG1. Liposomal encapsulation resulted in longer IgG2a/2b and IgG3 half-lives, especially when MDP-GDP was present in the liposome. These results demonstrate that, whereas MDP preferentially stimulates IgG1 antibodies, liposomes elicit high levels of IgG2a/2b isotypes with significantly longer serum half-lives.