Phillips N C, Gagné L, Ivanoff N, Riveau G
Faculté de pharmacie, Université de Montréal, Québec, Canada.
Vaccine. 1996 Jun;14(9):898-904. doi: 10.1016/0264-410x(96)82949-5.
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.
测定了磷脂组成对皮下注射脂质体牛血清白蛋白（BSA）、鼠单克隆抗体GK1.5（抗CD4）或来自HIV gp120第二个保守结构域的21个氨基酸肽后小鼠IgG抗体反应的影响，以及对口服脂质体曼氏血吸虫谷胱甘肽-S-转移酶（Sm28GST）后IgA、IgE和IgG抗体反应的影响。将抗体反应与明矾吸附的和N-乙酰胞壁酰-L-丙氨酰-D-异谷氨酰胺（MDP）-抗原混合物进行比较。对于皮下途径，二棕榈酰磷脂酰胆碱（DPPC）/二肉豆蔻酰磷脂酰甘油（DMPG）脂质体诱导产生54%-60%的IgG1和35%-44%的IgG(2a+2b)。DPPC/二棕榈酰磷脂酰乙醇胺（DPPE）脂质体诱导产生73%-78%的IgG1和15%-25%的IgG(2a+2b)。DPPC/磷脂酰丝氨酸（PS）脂质体诱导产生86%-89%的IgG1和8%-12%的IgG(2a+2b)。明矾和MDP诱导产生79%-91%的IgG1和4%-17%的IgG(2a+2b)。对于所有三种抗原，诱导IgG抗体的佐剂活性顺序为DPPC/DMPG>DPPC/PE>>明矾>>MDP>DPPC/PS。DPPC/DMPG脂质体是口服给药后诱导针对Sm28GST的分泌型IgA、循环型IgE和IgG抗体的唯一有效佐剂。脂质体-抗原混合物未能引发抗体反应表明，抗原的脂质体包封对于佐剂活性是必不可少的。这些结果表明，磷脂组成与佐剂活性之间的相关性与脂质体电荷、抗原或给药途径无关。
