Liposomal antigens

Rao M, et al. Trafficking of liposomal antigen to the trans-Golgi of murine macrophages requires both liposomal lipid and liposomal protein. Exp Cell Res 1999 246 203. 

Lutsiak CM, Sosnowski DL, Wishart DS, Kwon GS, Samuel J. Use of a liposome antigen deliveiy system to alter immune responses in vivo. J Pharm Sci 1998 87 1428-1432. 

Table 2, Blood type-determining antigens transferred from human erythrocyte to liposome. Antigens were assayed by each specific antibody (see text).

Adjuvants are substances which can modify the immune response of an antigen (139,140). With better understanding of the functions of different arms of the immune system, it is possible to explore the effects of an adjuvant, such that the protective efficacy of a vaccine can be improved. At present, aluminum salt is the only adjuvant approved for use in human vaccines. New adjuvants such as QS-21, 3D-MPL, MF-59, and other liposome preparations are being evaluated. Several of these adjuvants have been in clinical trial, but none have been approved for human use. IL-12 has been proposed as an adjuvant which can specifically promote T-helper 1 ceU response, and can be a very promising adjuvant for future vaccine development. 

The application of modified electrodes for the assay of antibodies in senun preparations using redox indicators encapsuled into antigene marked liposomes attached to an electrode surface was suggested First model studies towards this goal make use of ferricyanide ions entrapped in synthetic vesicles. 

Liposomes have been widely used as model membranes and their physicochemical properties have therefore been studied extensively. More recently, they have become important tools for the study of membrane-mediated processes (e.g., membrane fusion), catalysis of reactions occurring at interfaces, and energy conversion. Besides, liposomes are currently under investigation as carrier systems for drugs and as antigen-presenting systems to be used as vaccines. 

In vivo reproducible results can only be achieved if the liposome-drug or -antigen combinations are thoroughly characterized upon preparation in terms of their physical and chemical properties and, besides, if the stability during storage is ensured. In this chapter both the pharmaceutical (preparation, characterization, and stability) aspects and the therapeutic potentials and limitations of drug and antigen delivery with liposomes will be discussed. 

Thus, liposomes—with or without adjuvants—have a potential as antigen delivery systems. No clear insights exist on how to prepare liposome-based vaccines with optimum immunological properties by rationale instead of by trial and error. Therefore, much basic work is needed to unravel the mechanisms involved. 

Apart from liposomes, other vehicles for delivery of antigens to the immune system, such as iscoms, emulsions, and micellar structures, are presently under investigation (Jiskoot et al., 1986b Allison and Byars, 1986 Kersten et al., 1988a,b). 

Desiderio, J. V., and Campbell, S. G. (1985), Immunization against experimental murine salmonellosis with liposome-associated O-antigen. Inf. Inunun.. 48. 658-663. 

Rhalem, A., Bourdieu, C., Luffau, G., and Pery, P. (1988). Vaccination of mice with liposome-entrapped adult antigens of Nippo-strongylus brasiliensis. Ann. Inst. Pasteur/Immunol.. 139, 157-166. 

Schroit, A. J., and Key, M. E. (1983). Induction of syngeneic tumor-specific immunity by liposomes reconstituted with L2C tumor-cell antigens, Immunology. 49. 431-438. 

M. (1987). Tumor targeting potential of liposomes encapsulating Ga-67 and antibody to Dalton s lymphoma associated antigen (anti-DLAA), Int. J. Rad. Oncol. Biol. Phys.. 13, 1713-1719. 

In oncology, to study the relationship between the normal and the tumour cell, to detect tumour-associated antigens (CEA, carcino-embryonic antigen, and AFP, a-fetoprotein) and subsequently to enable cancer therapy to be monitored, to locate tumour metastases, and to deliver cytotoxic drugs, toxins, radionuclides, or liposomes to tumour cells. 

Complement induced immune lysis of cells and liposomes to release markers which are then detected electrochemically has been used to detect antibodies and antigens in a homogeneous format at nanomolar levels 252-256) qqjJj amperometric and potentio-metric electrodes have been employed. Unfortunately, major improvements in sensitivity appear unlikely, and instability of liposomes makes development of stable reagents for commercial systems difficult. 

The important attributes of liposomes as a drug carrier are (a) they are biologically inert and completely biodegradable (b) they pose no concerns of toxicity, antigenicity, or pyrogenicity, because phospholipids are natural components of all cell membranes (c) they can be prepared in various sizes, compositions, surface charges, and so forth, depending on the requirements of... 

Although most drugs are absorbed from the intestine by the blood capillary network in the villi, they can also be taken up by the lymphatic system (an integral and necessary part of the vascular system, the function of which is to collect extra tissue fluid and return it to the vascular compartment), particularly by M cells that reside in the Peyer s patch regions of the intestine. Peyer s patches have also been implicated in the regulation of the secretory immune response. Wachsmann et al. [277] reported that an antigenic material encapsulated within a liposome, when administered perorally, is taken up by these M cells and exhibited better saliva and serum IgA (primary and secondary)... 

Fig. 23 Saliva and serum IgA (primary and secondary) response following orally administered soluble antigen Streptococcus mutans cell wall extract (open circles, soluble antigen solid circles, liposome-encapsulated material) (phosphatidylcholine, phosphatidic acid, cholesterol). (From Ref. 277).

Copland MJ, Baird MA, Rades T et al (2003) Liposomal delivery of antigen to human dendritic cells. Vaccine 21 883-890... 

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