Liposomal cationic charge and antigen adsorption are important properties for the efficient deposition of antigen at the injection site and ability of the vaccine to induce a CMI response

被引:140
作者
Henriksen-Lacey, Malou [1 ]
Christensen, Dennis [2 ]
Bramwell, Vincent W. [1 ]
Lindenstrom, Thomas [2 ]
Agger, Else Marie [2 ]
Andersen, Peter [2 ]
Perrie, Yvonne [1 ]
机构
[1] Aston Univ, Sch Life & Hlth Sci, Birmingham B4 7ET, W Midlands, England
[2] Statens Serum Inst, DK-2300 Copenhagen, Denmark
关键词
Cationic liposomes; Protein antigen; Vaccine adjuvant; Pharmacokinetics; Immunostimulatory; ADJUVANT ACTIVITY; DENDRITIC CELLS; CORD FACTOR; PROTECTION; QUALITY; SYSTEMS; PROTEIN; MEMORY;
D O I
10.1016/j.jconrel.2010.03.027
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
With respect to liposomes as delivery vehicles and adjuvants for vaccine antigens, the role of vesicle surface charge remains disputed. In the present study we investigate the influence of liposome surface charge and antigen-liposome interaction on the antigen depot effect at the site of injection (SOI). The presence of liposome and antigen in tissue at the SOI as well as the draining lymphatic tissue was quantified to analyse the lymphatic draining of the vaccine components. Furthermore investigations detailing cytokine production and T-cell antigen specificity were undertaken to investigate the relationship between depot effect and the ability of the vaccine to induce an immune response. Our results suggest that cationic charge is an important factor for the retention of the liposomal component at the SOI, and a moderate to high (>50%) level of antigen adsorption to the cationic vesicle surface was required for efficient antigen retention in the same tissue. Furthermore, neutral liposomes expressing poor levels of antigen retention were limited in their ability to mediate long term (14 days) antigen presentation to circulating antigen specific T-cells and to induce the Th1 and Th17 arms of the immune system, as compared to antigen adsorbing cationic liposomes. The neutral liposomes did however induce the production of IL-5 at levels comparable to those induced by cationic liposomes, indicating that neutral liposomes can induce a weak Th2 response. (C) 2010 Elsevier B.V. All rights reserved.
引用
收藏
页码:102 / 108
页数:7
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