Engraftment of plasma membrane vesicles into liposomes: A new method for designing of liposome-based vaccines

Document Type: Original Article

Authors

1 Department of Immunology, Autoimmune Diseases Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

2 Department of Pharmaceutical Biotechnology Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran

3 School of Medicine, University of Sydney, Sydney, Australia

Abstract

Objective(s):One of the major challenges in the field of vaccine design is choosing immunogenic antigens which can induce a proper immune response against complex targets like malignant cells or recondite diseases caused by protozoan parasites such as leishmaniasis. The aim of this study was to find a way to construct artificial liposome-based cells containing fragments of target’s cell membrane. This structure not only mimics the real biological properties of proteins in the cell membrane of target cells, but also may induce the required immune responses, which culminate in eradication of target cells.
Materials and Methods: Five different techniques have been investigated to engraft the plasma membrane’s vesicles (PMVs) derived from a characterized Leishmania parasite into liposomes. The most efficient method was tested again on the PMVs derived from well-known breast cancer cell line SK-BR-3. The percentage of engraftment was determined by two-color flowcytometry after staining the engrafted dioctadecyl-3,3,3'3'-tetramethylindocarbocyanine DiI[FA1] -labeled liposomes with FITC-labeled PMVs.
Results: Among the investigated techniques, freeze-drying method with 91±2% and 90±3% of engraftment for Leishmania and SK-BR-3 derived PMVs, respectively, showed superiority over the other methods. In addition, after 9 weeks storage in refrigerator, freeze-dried fused particles kept their original size (660±350 nm) and fusion efficiency (94±3%).
Conclusion: Among five different engraftment techniques, freeze-drying is preferred over the other methods due to its simplicity, more fusion efficiency and stability of produced particles during storage.

Keywords


1. Okwor I, Liu D, Uzonna J. Qualitative differences in the early immune response to live and killed Leishmania major: Implications for vaccination strategies against Leishmaniasis. Vaccine 2009; 27:2554-2562.

2. Okwor I, Uzonna J. Vaccines and vaccination strategies against human cutaneous leishmaniasis. Hum Vaccin 2009; 5:291-301.

3. Northen H, Paterson GK, Constantino-Casas F, Bryant CE, Clare S, Mastroeni P, et al. Salmonella enterica serovar Typhimurium mutants completely lacking the F0F1 ATPase are novel live attenuated vaccine strains. Vaccine 2010; 28:940-949.

4. Rhorer J, Ambrose CS, Dickinson S, Hamilton H, Oleka NA, Malinoski FJ, et al. Efficacy of live attenuated influenza vaccine in children: A meta-analysis of nine randomized clinical trials. Vaccine 2009; 27:1101-1110.

5. Silvestre R, Cordeiro-da-Silva A, Ouaissi A. Live attenuated Leishmania vaccines: a potential strategic alternative. Arch Immunol Ther Exp (Warsz) 2008; 56:123-126.

6. VanBuskirk KM, O'Neill MT, De La Vega P, Maier AG, Krzych U, Williams J, et al. Preerythrocytic, live-attenuated Plasmodium falciparum vaccine candidates by design. Proc Natl Acad Sci 2009; 106:13004-13009.

7. Maciag PC, Radulovic S, Rothman J. The first clinical use of a live-attenuated Listeria monocytogenes vaccine: A Phase I safety study of Lm-LLO-E7 in patients with advanced carcinoma of the cervix. Vaccine 2009; 27:3975-3983.

8. Sporri R, Reis e Sousa C. Inflammatory mediators are insufficient for full dendritic cell activation and promote expansion of CD4+ T cell populations lacking helper function. Nat Immunol 2005; 6:163-170.

9. Foulds KE, Wu CY, Seder RA. Th1 memory: implications for vaccine development. Immunol Rev 2006; 211:58-66.

10. Copland MJ, Baird MA, Rades T, McKenzie JL, Becker B, Reck F, et al. Liposomal delivery of antigen to human dendritic cells. Vaccine 2003; 21:883-890.

11. Moribe K, Maruyama K. Pharmaceutical design of the liposomal antimicrobial agents for infectious disease. Curr Pharm Des 2002; 8:441-454.

12. Dubensky TW Jr, Reed SG. Adjuvants for cancer vaccines. Semin Immunol 2010; 22:155-161.

13. Sprott GD, Dicaire CJ, Gurnani K, Deschatelets LA, Krishnan L. Liposome adjuvants prepared from the total polar lipids of Haloferax volcanii, Planococcus spp. and Bacillus firmus differ in ability to elicit and sustain immune responses. Vaccine 2004; 22:2154-2162.

14. Alving CR. Immunologic aspects of liposomes: presentation and processing of liposomal protein and phospholipid antigens. Biochim Biophys Acta 1992; 1113:307-322.

15. Christensen D, Korsholm KS, Andersen P, Agger EM. Cationic liposomes as vaccine adjuvants. Expert Rev Vaccines 2011; 10:513-521.

16. Maurer N, Fenske DB, Cullis PR. Developments in liposomal drug delivery systems. Expert Opin Biol Ther 2001; 1:923-947.

17. Wilschut J. Influenza vaccines: the virosome concept. Immunol Lett 2009; 122:118-121.

18. Butts C, Maksymiuk A, Goss G, Soulières D, Marshall E, Cormier Y, et al. Updated survival analysis in patients with stage IIIB or IV non-small-cell lung cancer receiving BLP25 liposome vaccine (L-BLP25): phase IIB randomized, multicenter, open-label trial. J Cancer Res Clin Oncol 2011; 137:1337-1342.

19. Fries LF, Gordon DM, Richards RL, Egan JE, Hollingdale MR, Gross M, et al. Liposomal malaria vaccine in humans: a safe and potent adjuvant strategy. Proc Natl Acad Sci 1992; 89:358-362.

20. Reed SG, Bertholet S, Coler RN, Friede M. New horizons in adjuvants for vaccine development. Trends Immunol 2009; 30:23-32.

21. Kirby CJ, Gregoriadis G. Preparation of liposomes containing factor VIII for oral treatment of haemophilia. J Microencapsul 1984; 1:33-45.

22. Jett M, Seed TM, Jamieson GA. Isolation and characterization of plasma membranes and intact nuclei from lymphoid cells. J Biol Chem 1977; 252:2134-2142.

23. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976; 72:248-254.

24. Torchilin VP, Weissig V. Liposomes: a practical approach. 2nd ed. New York: Oxford University Press; 2003.

25. Kersten GF, Crommelin DJ. Liposomes and ISCOMS as vaccine formulations. Biochim Biophys Acta 1995; 1241:117-138.

26. Copland MJ, Rades T, Davies NM, Baird MA. Lipid based particulate formulations for the delivery of antigen. Immunol Cell Biol 2005; 83:97-105.

27. Nakanishi T, Kunisawa J, Hayashi A, Tsutsumi Y, Kubo K, Nakagawa S, et al. Positively charged liposome functions as an efficient immunoadjuvant in inducing immune responses to soluble proteins. Biochem Biophys Res Commun 1997; 240:793-797.

28. Badiee A, Khamesipour A, Samiei A, Soroush D, Shargh VH, Kheiri MT, et al. The role of liposome size on the type of immune response induced in BALB/c mice against leishmaniasis: rgp63 as a model antigen. Exp Parasitol 2012; 132:403-409.

29. Henriksen-Lacey M, Devitt A, Perrie Y. The vesicle size of DDA:TDB liposomal adjuvants plays a role in the cell-mediated immune response but has no significant effect on antibody production. J Control Release 2011; 154:131-137.

30. Gregoriadis G, Gursel I, Gursel M, McCormack B. Liposomes as immunological adjuvants and vaccine carriers. J Control Release 1996; 41:49-56.

31. Maeda T, Balakrishnan K, Mehdi SQ. A simple and rapid method for the preparation of plasma membranes. Biochim Biophys Acta 1983; 731:115-120.

32. Altin JG, Parish CR. Liposomal vaccines--targeting the delivery of antigen. Methods 2006; 40:39-52.

33. van Broekhoven CL, Altin JG. The novel chelator lipid 3(nitrilotriacetic acid)-ditetradecylamine (NTA(3)-DTDA) promotes stable binding of His-tagged proteins to liposomal membranes: potent anti-tumor responses induced by simultaneously targeting antigen, cytokine and costimulatory signals to T cells. Biochim Biophys Acta 2005; 1716:104-116.

34. Kaech SM, Wherry EJ, Ahmed R. Effector and memory T-cell differentiation: implications for vaccine development. Nat Rev Immunol 2002; 2:251-262.

35. Bhowmick S, Mazumdar T, Sinha R, Ali N. Comparison of liposome based antigen delivery systems for protection against Leishmania donovani. J Control Release 2010; 141:199-207.

36. Brewer JM, Tetley L, Richmond J, Liew FY, Alexander J. Lipid vesicle size determines the Th1 or Th2 response to entrapped antigen. J Immunol 1998; 161:4000-4007.

37. Fifis T, Gamvrellis A, Crimeen-Irwin B, Pietersz GA, Li J, Mottram PL, et al. Size-dependent immunogenicity: therapeutic and protective properties of nano-vaccines against tumors. J Immunol 2004; 173:3148-3154.