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Enhanced antibody response to liposome-associated protein antigens: preferential stimulation of IgG2a/b production
1Department of Medicine, McGill University, Montreal, Quebec, Canada.
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.
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.