Singh Sanjay K, Bisen Prakash S
Department of Biotechnology, J.C. Bose Institute of Life Sciences, Bundelkhand University, Jhansi 284218, U.P., India.
Vaccine. 2006 May 8;24(19):4161-6. doi: 10.1016/j.vaccine.2006.02.047. Epub 2006 Mar 20.
Present study aims to enhance the efficacy of liposomes as an adjuvant by steric protection and strengthen the path of vaccine research. PEG grafted liposomes carrying epitopes on their surface showed enhanced adjuvanticity than liposomes carrying epitopes for elicitation and prolongation of immune response to an antigenic epitope of gp41, a transmembrane protein of HIV-1. The multiples of epitope were incorporated onto the surface of liposomes by conjugating them with phosphatidylethanolamine that was used in the formulation of liposomes at an optimized ratio. Furthermore, the liposomes carrying epitopes on their surface were sterically protected by shielding with methoxy-poly(ethylene glycol), mass 20 kDa. Methoxy-poly(ethylene glycol) was activated to its electrophilic N-succinimide carbonate derivative, methoxy-poly(ethylene glycol)-N-succinimide carbonate, that formed a urethane linkage with the amino group of phosphatidylethanolamine. The epitope was covalently coupled to phosphatidylethanolamine through an amide bond between the -COOH group of the epitope and -NH2 group of phosphatidylethanolamine under the catalysis of 1-ethyl-3-(3-dimethylaminopropy-1)-carbodiimide. PEG grafted epitopes carrying liposomes showed about two times higher immune response and prolonged persistence of antibodies than that of liposomes carrying epitopes without PEG moieties.
本研究旨在通过空间位阻保护提高脂质体作为佐剂的功效，并加强疫苗研究的途径。表面携带表位的聚乙二醇接枝脂质体比携带表位的脂质体表现出更强的佐剂活性，能够引发和延长对HIV-1跨膜蛋白gp41抗原表位的免疫反应。通过将表位与磷脂酰乙醇胺以优化比例缀合，将多个表位整合到脂质体表面，磷脂酰乙醇胺用于脂质体制剂。此外，表面携带表位的脂质体通过用20 kDa的甲氧基聚（乙二醇）屏蔽进行空间位阻保护。甲氧基聚（乙二醇）被活化成其亲电的N-琥珀酰亚胺碳酸酯衍生物，即甲氧基聚（乙二醇）-N-琥珀酰亚胺碳酸酯，它与磷脂酰乙醇胺的氨基形成脲键。在1-乙基-3-（3-二甲基氨基丙基-1）-碳二亚胺的催化下，表位通过表位的-COOH基团与磷脂酰乙醇胺的-NH2基团之间的酰胺键与磷脂酰乙醇胺共价偶联。携带聚乙二醇接枝表位的脂质体比携带无聚乙二醇部分表位的脂质体表现出约两倍高的免疫反应和延长的抗体持久性。
