Liposomes adjuvant effect

Vanrooijen, N. and R. Vannieuwmegen, Endotoxin Enhanced Adjuvant Effect of Liposomes, Particularly When Antigen and Endotoxin Are Incorporated within the Same Liposome, Immunological Communications. 9, 747, 1980. 

Figure 6 Immunopotentiating reconstituted influenza virosomes (IRIV) adjuvant effects in the induction of tumor associated antigen-specific cytotoxic T cell. CD14-negative cells from a healthy donor peripheral blood mononuclear cells were cocultured with autologous immature dendritic cells (iDC) in the presence of Melan-A/Mart-l27-35, alone (A) or supplemented with either control liposomes (B) or IRIV (1 50, C). On day 7, culture cells were restimulated with Melan-A/MART-127-35 pulsed iDC and cultured for six further days [see Materials and Methods ]. On day 7 after restimulation cells were stained with fluorescein isothiocyanate-conjugated anti-CD8 and phosphatidylethanolamine-conjugated HL A-A0201 /Melan-A/MART -127-3 5 tetramers. Source From Ref. 6.

The influence of physicochemical properties of liposomes, such as charge density, membrane fluidity, and epitope density, on the immune response elicited by antigens has been extensively studied [37]. In addition to antigens, other immune stimulators that are amphoteric muramyl peptides or lipid-soluble compounds, such as monophosphoryl lipid A or muramyl tripeptidyl-phosphatidylethanolamine, can also be incorporated into liposomes to increase their adjuvant effect in eliciting immune responses [34]. 

Yasuda, T., Kanegasaki, Sh.f Tsumita, T., Tadakuma, T., Homma, 3.Y., Inage, M., Kusumoto, S., and Shiba, T. (1982). Biological activity of chemically synthesized lipid A analogues. Demonstration of adjuvant effect in hapten-sensitized liposomal system. Eur. 3. Biochem., 124, 405-007... 

Kim, Ch.K., Jeong, E.J. Development of dried liposomes as effective immuno-adjuvants for hepatitis B surface antigen. bit./. Pharm. 115,193-199,1995... 

Comparisons of antigen carrier systems have been the subject of many studies. The reported antigenic activity depends on the properties of the carrier systems such as their adjuvant effect and/or particle size, and viscosity. For a comparison to be valid, the systems being compared must show similar properties otherwise, the studies are misleading. Based on their properties, already it is evident that emulsion and liposome formulations offer more advantageous results. In our studies we found that multiple emulsions induce more antigenic activity than any cationic particle formulation with the classic subunit vaccine, and they enhance the immunization s efficacy (Bozkir et al, 2004). 

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 adjuvanticity of liposomes depends upon their composition, number of layers and charge characteristics. They act as effective adjuvants for both protein- and carbohydrate-based antigens and help stimulate both B- and T-cell responses. Their likely mode of action includes depot formation, but they also possibly increase/enhance antigen presentation to macrophages. The exact molecular mechanism(s) by which they stimulate a T-cell response remains to be elucidated,... 

Roth A, et al. Synthesis of thiol-reactive lipopeptide adjuvants. Incorporation into liposomes and study of their mitogenic effect on mouse splenocytes. Bioconjugate Chem 2004 15 541. 

Liposomal formulations may also be used to deliver TLR4 agonists. Consisting of spherical vesicles formed by the self-assembly of phospholipid bilayers, liposomes are a versatile, biocompatible vaccine adjuvant formulation. The wide variety of available phospholipid molecules that are employed to make liposomes may have significant effects on the structure and biological activity of the adjuvant. 

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