Influence of phospholipid composition on antibody responses to liposome encapsulated protein and peptide antigens.
The effect of phospholipid composition on mouse IgG antibody responses to liposomal bovine serum albumin (BSA), murine monoclonal antibody GK1.5 (anti-CD4) or a 21 amino acid peptide from the second conserved domain of HIV gp120 after s.c. administration, and on the IgA, IgE, and IgG antibody response to liposomal Shistosoma mansoni glutathione-S-transferase (Sm28GST) after oral administration, was determined. Antibody responses were compared with alum-adsorbed and N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP)-antigen mixtures. For the s.c. route, dipalmitoylphosphatidylcholine (DPPC)/dimyristoylphosphatidylglycerol (DMPG) liposomes induced 54-60% IgG1 and 35-44% IgG(2a+2b). DPPC/dipalmitoylphosphatidylethanolamine (DPPE) liposomes induced 73-78% IgG1 and 15-25% IgG(2a+2b). DPPC/ phosphatidylserine (PS) liposomes induced 86-89% IgG1 and 8-12% IgG(2a+2b). Alum and MDP induced 79-91% IgG1 and 4-17% IgG(2a+2b). The rank order of adjuvanticity for induction of IgG antibody was DPPC/DMPGDPPC/PE > > alum > > MDPDPPC/PS for all three antigens. DPPC/DMPG liposomes were the only effective adjuvant for the induction of secretory IgA and circulatory IgE and IgG antibodies against Sm28GST after oral administration. The failure of liposome-antigen mixtures to elicit an antibody response showed that liposomal incorporation of the antigens was obligatory for adjuvant activity. These results demonstrate that the correlation between phospholipid composition and adjuvanticity is independent of liposome charge, antigen, or route of administration.
Phillips
N C
NC
Faculté de pharmacie, Université de Montréal, Québec, Canada.
Gagné
L
L
Ivanoff
N
N
Riveau
G
G
D000276:Adjuvants, Immunologic / Q000737:chemistry; D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D000941:Antigens / Q000276:immunology*; D005260:Female; D007070:Immunoglobulin A / Q000096:biosynthesis; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis*; D008081:Liposomes / Q000737:chemistry* / Q000276:immunology* / Q000633:toxicity; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology*; D010743:Phospholipids / Q000032:analysis* / Q000276:immunology*; D011506:Proteins / Q000276:immunology*; D012710:Serum Albumin, Bovine / Q000276:immunology
D000276:Adjuvants, Immunologic; D000941:Antigens; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008081:Liposomes; D010455:Peptides; D010743:Phospholipids; D011506:Proteins; D012710:Serum Albumin, Bovine; D007073:Immunoglobulin E