Liposomal vaccines

Development of a Liposomal Vaccination System for Immunity-Modulating Antitumor Therapy... 

In Vitro Characterization and Optimization of the Liposomal Vaccine System by FACS Analysis... 

Influence of the Liposomal Vaccine System on the Number of Activated Circulating Cytotoxic T Cells... 

It can be clearly seen in Figure 5 that the liposomal vaccination had a dramatic effect on the number of activated CTL at day 1 (5.4% cells activated) and day 2 (4.1% cells activated). Free TRP-2 together with free CpG showed at even 10 times higher concentration no visible vaccination power (comparable to pure buffer administration). 

Test for the Prophylactic and Therapeutic Efficiency of the Liposomal Vaccine System... 

The prophylactic antitumor efficiency was tested by injecting 12 mice twice in seven days with AVE 3 TRP-2 (10 pg TRP-2) and AVE 3 1826 CpG (1.3 pg CpG) intradermally the control group remained untreated. Seven days after the last immunization 2 x 10 B16 tumor cells in 200 pL HBSS were injected into the tail vein of each mouse. Twenty days after tumor inoculation, the animals were sacrificed and the metastases in the prepared lungs counted. As Table 2 shows, the liposomal vaccination has a significant effect on the tumor growth in comparison to untreated animals. This is also reflected by the visual appearance of the lungs (data not shown). 

Li WM, Dragowska WH, Bally MB, Schutze-Redelmeier MP. Effective induction of CD8+ T-cell response using CpG oligodeoxynucleotides and HER-2/ neu-derived peptide co-encapsulated in liposomes. Vaccine 2003 21(23) 3319-3329. 

Clark, M. A., Blair, H., Liang L., et al. Targeting polymerized liposome vaccine carriers to intestinal M cells. Vaccine 20 208-217, 2001. 

Ann Clark M, Blair H, Liang L, Brey RN, Brayden D, Hirst BH (2001) Targeting polymerised liposome vaccine carriers to intestinal M cells. Vaccine 20(1-2) 208-217 Avtushenko SS, Sorokin EM, Zoschenkova NY, Naichin AN (1996) Clinical and immunological characteristics of the emulsion form of inactivated influenza vaccine delivered by oral immunization. J Biotechnol 44(1-3) 21-28 Aziz MA, Midha S, Waheed SM, Bhatnagar R (2007) Oral vaccines new needs, new possibilities. Bioessays 29(6) 591-604... 

Sutter RW, Prevots DR, Cochi SL (2000) Poliovirus vaccines - progress toward global poliomyelitis eradication and changing routine immunization recommendations in the United States. Pediatr Clin North Am 47(2) 287-308 Therien HM, Lair D, Shahum E (1990) Liposomal vaccine - influence of antigen association on the kinetics of the humoral response. Vaccine 8(6) 558-562 Thones N, Muller M (2007) Oral immunization with different assembly forms of the HPV 16 major capsid protein LI induces neutralizing antibodies and cytotoxic T-lymphocytes. Virol 369(2) 375-388... 

Aramaki, Y., Fujii, Y., Yachi, K., Kikuchi, H., and Tsuchiya, S. (1994), Activation of systemic and mucosal immune response following nasal administration of liposomes, Vaccine, 12,1241-1245. 

From 1984, when they were first developed, DRV liposomes have been used for liposomal encapsulation of various active substances which may be divided into three main categories (1) Low MW drug molecules (mainly hydrophilic drugs) (3-20) (2) Proteins or peptides and enzymes (21-26), and (3) DNA or oligonucleotides (26-32). From these categories, the last two are primarily used as liposomal vaccines. Some examples of substances entrapped in DRV liposomes from the last 10 year literature are presented in Table 1. 

After this, special considerations and methodologies that should be applied for encapsulation of other types of molecules or for special types of applications (liposomal vaccines) will be given in detail. 

Here, we present methods of preparation of liposomal vaccines and results obtained in our laboratories with small unilamellar liposomes as carriers of antigen peptides and peptide encoding DNA plasmids, demonstrating their high potential as therapeutic vaccine formulations against infectious diseases and cancers. 

We do not describe in details the immunological methods (immunization, Gr release assay, ELISPOT, ELISA and flow cytometry) used for the analysis of the immune responses induced by the liposome vaccines (Subheading 3.2). For comprehensive information, we refer to our publications (21-23) and to the related literature. 

Peptide liposome vaccines were prepared by freeze-thawing of the lipid/peptide mixtures followed by sequential filter extrusion. 

If the liposome vaccines are intended to be stored for longer periods of time, they may be frozen or lyophilized, provided... 

Altin JG, Parish CR (2006) Liposomal vaccines - targeting the delivery of antigen. Methods 40 39-52... 

Griffiths, G.D., Phillips, G.J. and Bailey, S.C. (1999) Comparison of the quality of protection elicited by toxoid and peptide liposomal vaccine formulations against ricin as assessed by markers of inflammation. Vaccine, 17, 2562-2568. 

Michaeli, D. Grimes, S. Barenholz, Y. Even-Chen, S. Liposomal Vaccine. USPTO Application 20070082043 (White Case LLP Patent Department, New York, NY, USA), April 12, 2007. 

---