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Designing Liposomes as Vaccine Adjuvants

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Immunomic Discovery of Adjuvants and Candidate Subunit Vaccines

Part of the book series: Immunomics Reviews: ((IMMUN,volume 5))

Abstract

The most important perquisite in modern-day prophylactic vaccine development is the production of safe, nonreverting vaccines. To do this there has been a distinct move towards peptide or protein antigen-based vaccines, which are incapable of becoming virulent or mutating. However, whilst such vaccines appear desirable on paper, they are generally poorly immunogenic. Consequently, there has been intense development in the field of adjuvants and delivery systems, which are capable of fulfilling two important functions: firstly that antigen is delivered to an immunologically relevant cell, and secondly that antigen is recognised as being immunogenic and subsequently processed.

Whilst many adjuvants are successful at ticking one of these parameters, few can act as the combined immunostimulatory delivery systems. Liposomes are among some of the successful formulations, which have been pursued as clinically relevant adjuvants (equally there are many liposome formulations which have been ignored due to their inability to be both delivery vehicle and immunostimulatory). However, in this chapter we will focus on the successful design of adjuvantal liposomes, which are of interest to vaccine developers focusing on life-threatening diseases of both the developing and developed world. Particular emphasis will be given to structural considerations and how varying these have an effect on the observed immunological outcome, measured in either in vitro, in vivo or ex vivo studies.

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References

  1. Agger EM, Rosenkrands I et al (2008) Cationic liposomes formulated with synthetic mycobacterial cordfactor (CAF01): a versatile adjuvant for vaccines with different immunological requirements. PLoS One 3(9):e3116

    Article  PubMed  Google Scholar 

  2. Agrawal B, Krantz MJ et al (1998) Rapid induction of primary human CD4+ and CD8+ T cell responses against cancer-associated MUC1 peptide epitopes. Int Immunol 10(12):1907–1916

    Article  PubMed  CAS  Google Scholar 

  3. Andersen CAS, Rosenkrands I et al (2009) Novel generation mycobacterial adjuvant based on liposome-encapsulated monomycoloyl glycerol from mycobacterium bovis bacillus calmette-guérin. J Immunol 183:2294–2302

    Article  PubMed  CAS  Google Scholar 

  4. Arora A, Prausnitz MR et al (2008) Micro-scale devices for transdermal drug delivery. Int J Pharm 364(2):227–236

    Article  PubMed  CAS  Google Scholar 

  5. Bakouche O, Gerlier D (1986) Enhancement of immunogenicity of tumour virus antigen by liposomes: the effect of lipid composition. Immunology 58:507–513

    PubMed  CAS  Google Scholar 

  6. Ben Haij N, O Mzoughi, et al (2012) Cationic nanoglycolipidic particles as vector and adjuvant for the study of the immunogenicity of SIV Nef protein. Int J Pharm 423(1):116–123

    Article  PubMed  CAS  Google Scholar 

  7. Bernstein DI, Farley N et al (2010) The adjuvant CLDC increases protection of a herpes simplex type 2 glycoprotein D vaccine in guinea pigs. Vaccine 28:3748–3753

    Article  PubMed  CAS  Google Scholar 

  8. Bhowruth V, Minnikin DE et al (2009) Adjuvant properties of a simplified C32 monomycolyl glycerol analogue. Bioorg Med Chem Lett 19:2029–2032

    Article  PubMed  CAS  Google Scholar 

  9. Calcagnile S, Zuccotti G (2008) The virosomal adjuvanted influenza vaccine. Expert Opin Biol Ther 10(2):191–200

    Article  Google Scholar 

  10. Cevc G, Vierl U (2010) Nanotechnology and the transdermal route. A state of the art review and critical appraisal. J Control Release 141:277–299

    Article  PubMed  CAS  Google Scholar 

  11. Chadwick S, Kriegel C et al (2010) Nanotechnology solutions for mucosal immunization. Adv Drug Deliv Rev 62(4–5):394–407

    Article  PubMed  CAS  Google Scholar 

  12. Chen W, Yan W et al (2008) A simple but effective cancer vaccine consisting of an antigen and a cationic lipid. Cancer Immunol Immunother 57:517–530

    Article  PubMed  CAS  Google Scholar 

  13. Cheng J-Y, Huang H-N et al (2009) Transcutaneous immunization by lipoplex-patch based DNA vaccines is effective vaccination against japanese encephalitis virus infection. J Control Release 135:242–249

    Article  PubMed  CAS  Google Scholar 

  14. Christensen D, Foged C et al (2010) CAF01 liposomes as a mucosal vaccine adjuvant: in vitro and in vivo investigations. Int J Pharm 390:19–24

    Article  PubMed  CAS  Google Scholar 

  15. Christensen D, Korsholm KS et al (2007) Cationic liposomes as vaccine adjuvants. Expert Rev Vaccines 6(5):785–796

    Article  PubMed  CAS  Google Scholar 

  16. Gall D (1966) The adjuvant activity of aliphatic nitrogenous bases. Immunology 11:369–386

    PubMed  CAS  Google Scholar 

  17. Garçon N, Chomez P et al (2007) GlaxoSmithKline adjuvant systems in vaccines: concepts, achievements and perspectives. Expert Rev Vaccines 6(5):723–739

    Article  PubMed  Google Scholar 

  18. Hansen J, Jensen KT et al (2008) Liposome delivery of Chlamydia muridarum major outer membrane protein primes a Th1 response that protects against genital chlamydial infection in a mouse model. J Infect Dis 198:758–767

    Article  PubMed  CAS  Google Scholar 

  19. Henriksen-Lacey M, Bramwell VW et al (2009) Liposomes based on dimethyldioctadecylammonium promote a depot effect and enhance immunogenicity of soluble antigen. J Control Release 142(2):180–186

    Article  PubMed  Google Scholar 

  20. Henriksen-Lacey M, A Devitt, et al (2011) 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 154(2):131–137

    Article  PubMed  CAS  Google Scholar 

  21. Hiszczyńska-Sawicka E, Li H et al (2010) Comparison of immune response in sheep immunized with DNA vaccine encoding Toxoplasma gondii GRA7 antigen in different adjuvant formulations. Exp Parasitol 124:365–372

    Article  PubMed  Google Scholar 

  22. Ishii KJ, Koyama S et al (2008) Host innate immune receptors and beyond: making sense of microbial infections. Cell Host Microbe 3:352–363

    Article  PubMed  CAS  Google Scholar 

  23. Jacquet A, Vanderschrick J-F et al (2006) Vaccination with the recombinant allergen ProDer p 1 complexed with the cationic lipid DiC14-amidine prevents allergic responses to house dust mite. Mol Ther 11(6):960–968

    Article  Google Scholar 

  24. Johansen P, Mohanan D et al (2010) Lympho-geographical concepts in vaccine delivery. J Control Release 148(1):56–62

    Article  PubMed  CAS  Google Scholar 

  25. Joseph A, Itskovitz-Cooper N et al (2006) A new intranasal influenza vaccine based on a novel polycationic lipid-ceramide carbamoyl-spermine (CCS): i. immunogenicity and efficacy studies in mice. Vaccine 24(18):3990–4006

    Article  PubMed  CAS  Google Scholar 

  26. Kawai T, Akira S (2010) The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol 11(5):373–384

    Article  PubMed  CAS  Google Scholar 

  27. Kirby C, Gregoriadis G (1984) Dehydration-rehydration vesicles: a simple method for high yield drug entrapment in liposomes. Biotechnol 2:979–984

    Article  CAS  Google Scholar 

  28. Kufer TA, Sansonetti PJ (2011) NLR functions beyond pathogen recognition. Nat Immunol 12(2):121–128

    Article  PubMed  CAS  Google Scholar 

  29. Lay M, Callejo B et al (2009) Cationic lipid/DNA complexes (JVRS-100) combined with influenza vaccine (Fluzone®) increases antibody response, cellular immunity, and antigenically drifted protection. Vaccine 27:3811–3820

    Article  PubMed  CAS  Google Scholar 

  30. Logue CH, Phillips AT et al (2010) Treatment with cationic liposome-DNA complexes (CLDCs) protects mice from lethal Western equine encephalitis virus (WEEV) challenge. Antiviral Res 87:195–203

    Article  PubMed  CAS  Google Scholar 

  31. Lonez C, Lensink MF et al (2009) Cationic lipids activate cellular cascades. Which receptors are involved? Biochim Biophys Acta 1790(6):425–430

    Article  PubMed  CAS  Google Scholar 

  32. Mannock DA, Lee MYT et al (2008) Comparative calorimetric and spectroscopic studies of the effects of cholesterol and epicholesterol on the thermotropic phase behaviour of dipalmitoylphosphatidylcholine bilayer membranes. Biochim Biophys Acta 1778(10):2191–2202

    Article  PubMed  CAS  Google Scholar 

  33. Mohanan D, Slütter B et al (2010) Administration routes affect the quality of immune responses: a cross-sectional evaluation of particulate antigen-delivery systems. J Control Release 147(3):342–349

    Article  PubMed  CAS  Google Scholar 

  34. Morrey JD, Motter NE et al (2011) Breaking B and T cell tolerance using cationic lipid-DNA complexes (CLDC) as a vaccine adjuvant with hepatitis B virus (HBV) surface antigen in transgenic mice expressing HBV. Antiviral Res 90(3):227–230

    Article  PubMed  CAS  Google Scholar 

  35. Nakano Y, Mori M et al (2002) Cholesterol inclusion in liposomes affects induction of antigen-specific IgG and IgE antibody production in mice by a surface-linked liposomal antigen. Bioconjug Chem 13:744–749

    Article  PubMed  CAS  Google Scholar 

  36. Neutra M, Kozlowski P (2006) Mucosal vaccines: the promise and the challenge. Nat Rev Immunol 6:148–158

    Article  PubMed  CAS  Google Scholar 

  37. Nordly P, Rose F et al (2011) Immunity by formulation design: induction of high CD8+ T-cell responses by poly(I:C) incorporated into the CAF01 adjuvant via a double emulsion method. J Control Release 150(3):307–317

    Article  PubMed  CAS  Google Scholar 

  38. O’Hagan DT, Gregorio ED (2009) The path to a successful vaccine adjuvant—the long and winding road. Drug Discov Today 14(11/12):541–551

    Article  PubMed  Google Scholar 

  39. Perrie Y, Rades T (2012) FASTtrack: pharmaceutics—drug delivery and targeting. Second Edition. London: Pharmaceutical Press

    Google Scholar 

  40. Pestano LA, B. Christian, et al. (2011). ONT-10, a liposomal vaccine targeting hypoglycosylated MUC1, induces a potent cellular and humoral response and suppresses the growth of MUC1 expressing tumors. Proceedings of the 102nd annual meeting of the american association for cancer research. Orlando, Florida, Philadelphia (PA): AACR

    Google Scholar 

  41. Sharp FA, Ruane D et al (2009) Uptake of particulate vaccine adjuvants by dendritic cells activates the NALP3 inflammasome. Proc Natl Acad Sci U S A 160(3):870–875

    Article  Google Scholar 

  42. Shrivastava S, Lole KS et al (2009) Development of candidate combination vaccine for hepatitis E and hepatitis B: a liposome encapsulation approach. Vaccine 27:6582–6588

    Article  PubMed  CAS  Google Scholar 

  43. Sullivan SM, Doukas J et al (2010) Vaxfectin: a versatile adjuvant for plasmid DNA- and protein-based vaccines. Expert Opin Drug Deliv 7(12):1433–1446

    Article  PubMed  CAS  Google Scholar 

  44. Tanaka T, Legat A et al (2008) DiC14-amidine cationic liposomes stimulate myeloid dendritic cells through Toll-like receptor 4. Eur J Immunol 38:1–17

    Article  CAS  Google Scholar 

  45. Thomann J-S, Heurtault B et al (2011) Antitumor activity of liposomal ErbB2/HER2 epitope peptide-based vaccine constructs incorporating TLR agonists and mannose receptor targeting. Biomaterials 32(20):4574–4583

    Article  PubMed  CAS  Google Scholar 

  46. Troyer RM, Propst KL et al (2009) Mucosal immunotherapy for protection from pneumonic infection with Francisella tularensis. Vaccine 27:4424–4433

    Article  PubMed  CAS  Google Scholar 

  47. van Houte AJ, Snippe H et al (1981) Characterization of immunogenic properties of haptenated liposomal model membranes in mice. V. Effect of membrane composition on humoral and cellular immunogenicity. Immunology 44(3):561–568

    PubMed  Google Scholar 

  48. Voltan R, Castaldello A et al (2009) Priming with a very low dose of DNA complexed with cationic block copolymers followed by protein boost elicits broad and long-lasting antigen-specific humoral and cellular responses in mice. Vaccine 27(33):4498–4507

    Article  PubMed  CAS  Google Scholar 

  49. Wang D, Xu J et al (2010) Liposomal oral DNA vaccine (mycobacterium DNA) elicits immune response. Vaccine 28:3134–3142

    Article  PubMed  CAS  Google Scholar 

  50. Yan W, Huang L (2009) The effects of salt on the physicochemical properties and immunogenicity of protein based vaccine formulated in cationic liposome. Int J Pharm 368:56–62

    Article  PubMed  CAS  Google Scholar 

  51. Zhong Z, Wei X et al (2010) A novel liposomal vaccine improves humoral immunity and prevents tumor pulmonary metastasis in mice. Int J Pharm 399(1–2):156–162

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Yvonne Perrie .

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Henriksen-Lacey, M., Perrie, Y. (2013). Designing Liposomes as Vaccine Adjuvants. In: Flower, D., Perrie, Y. (eds) Immunomic Discovery of Adjuvants and Candidate Subunit Vaccines. Immunomics Reviews:, vol 5. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5070-2_10

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