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 G K1.5 (anti-CD4) or a 21 amino acid peptide from the second conserved d omain of HIV gp120 after s.c. administration, and on the IgA, IgE, and IgG antibody response to liposomal Shistosoma mansoni glutathione-S-t ransferase (Sm28GST) after oral administration, was determined. Antibo dy responses were compared with alum-adsorbed and N-acetylmuramyl-L-al anyl-D-idoglutamine (MDP)-antigen mixtures. For the s.c. route, dipalm itoylphosphatidylcholine (DPPC)/dimyristoylphosphatidylglycerol (DMPG) liposomes induced 54-60% IgG(1) and 35-44% IgG(2a+2b). DPPC/dipalmito ylphosphatidyl-ethanolamine (DPPE) liposomes induced 73-78% IgG(1) and 15-25% IgG(2a+2b). DPPC/phosphatidylserine (PS) liposomes induced 86- 89% IgG(l) and 8-12% IgG(2a+2b). Alum and MDP induced 79-91% IgG(l) an d 4-17% IgG(2a+2b). The rank order of adjuvanticity for induction of I gG antibody was DPPC/DMPGDPPClPE much greater than alum much greater t han MDPDPPC/PS for all three antigens. DPPC/DMPG liposomes were the on ly effective adjuvant for the induction of secretory IgA and circulato ry IgE and IgG antibodies against Sm28GST after oral administration. T he failure of liposome-antigen mixtures to elicit an antibody response showed that liposomal incorporation of the antigens was obligatory fo r adjuvant activity. These results demonstrate that the correlation be tween phospholipid composition and adjuvanticity is independent of lip osome charge, antigen, or route of administration. Copyright (C) 1996 Elsevier Science Ltd.