Immune response liposomes

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. 

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)... 

Shek, P.N., and Heath, T.D. (1983) Immune response mediated by liposome-associated protein antigens. 

Shek, P.N., and Sabiston, B.H. (1982b) Immune response mediated by liposome-associated protein antigens. II. Comparison of the effectiveness of vesicle-entrapped and surface-associated antigens in immu-nopotentiation. Immunology 47, 627. 

A variety of lipid adjuvants and protein mediators have also been shown to influence the immune response to antigens encapsulated in liposomes. The most widely used examples of such adjuvants for practical immunization procedures are endotoxin (including lipid A and lipopolysaccharide) and numerous types of lipophilic derivatives of muramyl dipeptide. 

The mode of association of peptides to liposome carriers might also be critical to induce a preferential immune response either humoral or cell mediated. For example, using a human mucin MUCl 20-mer peptide, it was found that only the physical association of the peptide to liposomes (either encapsulated or surface exposed after anchoring) was necessary to observe a cell-mediated response (34). In line with this observation, it was recently shown that a soluble peptide, representing a Melan-A/MART-1 tumor-associated antigen, when encapsulated into sterically stabilized liposomes, was able to stimulate a CTL response and this construct represented a suitable formulation for a specific tumor immunotherapy (69). In contrast, and in agreement with other studies (16), only the liposome surface exposed... 

Finally, besides conventional liposomes that are made from natural (e.g., egg yolk and soybean) or synthetic phospholipids, novel liposomes called archaeosomes that are prepared from the polar ether lipids extracted from various archaeobacteria proved also interesting for the design of vaccines as peptide antigen carriers (71) and as powerful self-adjuvanting vaccine delivery vesicles that promote both humoral and cell-mediated immunity (72). Related to this, one can mention that pseudopeptides, which are less prone to proteolysis when conjugated to liposomes, were also competent in triggering a humoral immune response (73). 

Friede M, et al. Induction of immune response against a short synthetic peptide antigen coupled to small neutral liposomes containing monophosphoryl lipid A. Mol Immunol 1993 30 539. 

Guan HH, et al. Liposomal formulations of synthetic MUCl peptides effects of encapsulation versus surface display of peptides on immune responses. Bioconjugate Chem 1998 9 451. 

Fernandes I, et al. Synthetic lipopeptides incorporated in liposomes in vitro stimulation of the proliferation of murine splenocytes and in vivo induction of an immune response against a peptide antigen. Mol Immunol 1997 34 569. 

Tosi PF, Radu D, Nicolau C. Immune response against the murine MDRI protein induced by vaccination with synthetic lipopeptides in liposomes. Biochem Biophys Res Commun 1995 212 494. 

It can therefore be concluded that immunization with liposomes containing both DNA and the encoded antigen leads to superior immune responses when compared with liposomes entrapping the DNA or protein vaccine alone. 

To review, in an experimental mouse model, LPDI/E7 vaccination both prevents the establishment of metastatic E7-expressing tumors in naive mice through an induced E7-specific T-cell immune response and, in mice with previously established E7-expressing tumors, causes tumor regression with one subcutaneous injection of LPDI/E7 [Han SJ, et al. Subcutaneous antigen loading of dendritic cells by liposome-protamine-DNA (LPD) nanoparticles results in their activation and induction of specific antitumor immune response (impublished)]. A robust immune response follows administration of LPDI/ peptide particles, which can be used as either a preventative or therapeutic cancer vaccination strategy due to the ability of the particles to prevent and eliminate tumors, respectively, in mouse models. 

These are an example of a nonviral vector that can accept large DNA inserts. Because the liposome lacks peptides, it does not provoke an immune response. The primary disadvantage is that, unlike viruses, the integration rate of liposome-contained DNA is very low. 

Depending on their size and surface charge, parenterally administered liposomes interact with the reticuloendothelial system (RES) and provoke an immune response. 

Therefore, liposomes, and also nanoparticles, may allow for the development of needle-less vaccination systems. Studies on mice inoculated with influenza DNA vaccine complexes with liposomes and SLN already demonstrated a clear T-cell (predominantly Thl-type) response. Therefore, the immune response appears to be mediated by Langerhans cells, which is the immune competent cell in the skin (for review, see [65]). 

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