Liposome-based adjuvants for subunit vaccines: Formulation strategies for subunit antigens and immunostimulators

Pharmaceutics

Volumn 8, Issue 1, 2016, Pages

  Schmidt, Signe Tandrup ^a,b   Foged, Camilla ^a   Korsholm, Karen Smith ^b   Rades, Thomas ^a   Christensen, Dennis ^b  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

^b STATENS SERUM INSTITUT   (Denmark)

Author keywords

Antigen; Formulation; Immunostimulator; Liposome; Vaccine adjuvant

Indexed keywords

ANTIGEN; CANCER VACCINE; CPG OLIGODEOXYNUCLEOTIDE; DIMYRISTOYLPHOSPHATIDYLGLYCEROL; DIPALMITOYLPHOSPHATIDYLCHOLINE; EARLY SECRETORY ANTIGENIC TARGET 6; EPIDERMAL GROWTH FACTOR RECEPTOR 2; GAG PROTEIN; HEPATITIS A VACCINE; HOUSE DUST ALLERGEN; HUMAN IMMUNODEFICIENCY VIRUS VACCINE; IMIQUIMOD; IMMUNOLOGICAL ADJUVANT; IMMUNOSTIMULATING AGENT; INFLUENZA VACCINE; LIPID; LIPOSOME; MALARIA VACCINE; MYCOBACTERIUM VACCINE; OVALBUMIN; PATTERN RECOGNITION RECEPTOR; PHOSPHORYL LIPID A; PLASMID DNA; POLYINOSINIC POLYCYTIDYLIC ACID; PROTEIN E7; SUBUNIT VACCINE; TECEMOTIDE; TOLL LIKE RECEPTOR 4; TOLL LIKE RECEPTOR 5; UNINDEXED DRUG;

ALLERGIC ASTHMA; ANTIBODY RESPONSE; ANTIGEN PRESENTING CELL; BREAST CANCER; CPG ISLAND; DRUG DELIVERY SYSTEM; DRUG DOSAGE FORM COMPARISON; DRUG FORMULATION; ENCAPSULATION; HEPATITIS A; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; HYDROPHOBICITY; IMMUNE RESPONSE; INFLUENZA; LIPID BILAYER; LUNG CANCER; MALARIA; NON SMALL CELL LUNG CANCER; NONHUMAN; PARTICLE SIZE; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PHYSICAL CHEMISTRY; REVIEW; SURFACE CHARGE; TUBERCULOSIS;

EID: 84961156254     PISSN: None     EISSN: 19994923     Source Type: Journal    
DOI: 10.3390/pharmaceutics8010007     Document Type: Review

References (119)

1. Rappuoli, R.; Miller, H.I.; Falkow, S. The intangible value of vaccination. Science 2002, 297, 937–939. [CrossRef] [PubMed]
2. Rappuoli, R. Bridging the knowledge gaps in vaccine design. Nat. Biotech. 2007, 25, 1361–1366. [CrossRef] [PubMed]
3. Di Pasquale, A.; Preiss, S.; Tavares Da Silva, F.; Garçon, N. Vaccine adjuvants: From 1920 to 2015 and beyond. Vaccines 2015, 3, 320–343. [CrossRef] [PubMed]
4. Zepp, F. Principles of vaccine design—lessons from nature. Vaccine 2010, 28 (Suppl. 3), C14–C24. [CrossRef] [PubMed]
5. Dey, A.K.; Srivastava, I.K. Novel adjuvants and delivery systems for enhancing immune responses induced by immunogens. Expert Rev. Vaccines 2010, 10, 227–251. [CrossRef] [PubMed]
6. Petrovsky, N.; Aguilar, J.C. Vaccine adjuvants: Current state and future trends. Immunol. Cell Biol. 2004, 82, 488–496. [CrossRef] [PubMed]
7. Perrie, Y.; Mohammed, A.R.; Kirby, D.J.; McNeil, S.E.; Bramwell, V.W. Vaccine adjuvant systems: Enhancing the efficacy of sub-unit protein antigens. Int. J. Pharm. 2008, 364, 272–280. [CrossRef] [PubMed]
8. Mohan, T.; Verma, P.; Rao, D.N. Novel adjuvants & delivery vehicles for vaccines development: A road ahead. Indian J. Med. Res. 2013, 138, 779–795. [PubMed]
9. Kamath, A.T.; Mastelic, B.; Christensen, D.; Rochat, A.-F.; Agger, E.M.; Pinschewer, D.D.; Andersen, P.; Lambert, P.-H.; Siegrist, C.-A. Synchronization of dendritic cell activation and antigen exposure is required for the induction of th1/th17 responses. J. Immunol. 2012, 188, 4828–4837. [CrossRef] [PubMed]
10. de Titta, A.; Ballester, M.; Julier, Z.; Nembrini, C.; Jeanbart, L.; van der Vlies, A.J.; Swartz, M.A.; Hubbell, J.A. Nanoparticle conjugation of cpg enhances adjuvancy for cellular immunity and memory recall at low dose. Proc. Natl. Acad. Sci. USA 2013, 110, 19902–19907. [CrossRef] [PubMed]
11. Tighe, H.; Takabayashi, K.; Schwartz, D.; Marsden, R.; Beck, L.; Corbeil, J.; Richman, D.D.; Eiden, J.J., Jr.; Spiegelberg, H.L.; Raz, E. Conjugation of protein to immunostimulatory DNA results in a rapid, long-lasting and potent induction of cell-mediated and humoral immunity. Eur. J. Immunol. 2000, 30, 1939–1947. [CrossRef]
12. Nordly, P.; Madsen, H.B.; Nielsen, H.M.; Foged, C. Status and future prospects of lipid-based particulate delivery systems as vaccine adjuvants and their combination with immunostimulators. Expert Opin. Drug Deliv. 2009, 6, 657–672. [CrossRef] [PubMed]
13. Bangham, A.D. Lipid bilayers and biomembranes. Annu. Rev. Biochem. 1972, 41, 753–776. [CrossRef] [PubMed]
14. Lasic, D.D. Novel applications of liposomes. Trends Biotechnol. 1998, 16, 307–321. [CrossRef]
15. Allison, A.C.; Gregoriadis, G. Liposomes as immunological adjuvants. Nature 1974, 252, 252–252. [CrossRef] [PubMed]
16. Perrie, Y.; Crofts, F.; Devitt, A.; Griffiths, H.R.; Kastner, E.; Nadella, V. Designing liposomal adjuvants for the next generation of vaccines. Adv. Drug Deliv. Rev. 2015. [CrossRef] [PubMed]
17. Schwendener, R.A. Liposomes as vaccine delivery systems: A review of the recent advances. Ther. Adv. Vaccines 2014, 2, 159–182. [CrossRef] [PubMed]
18. Badiee, A.; Khamesipour, A.; Samiei, A.; Soroush, D.; Shargh, V.H.; Kheiri, M.T.; Barkhordari, F.; Robert Mc Master, W.; Mahboudi, F.; Jaafari, M.R. 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. [CrossRef] [PubMed]
19. 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. [CrossRef] [PubMed]
20. Nakanishi, T.; Kunisawa, J.; Hayashi, A.; Tsutsumi, Y.; Kubo, K.; Nakagawa, S.; Fujiwara, H.; Hamaoka, T.; Mayumi, T. Positively charged liposome functions as an efficient immunoadjuvant in inducing immune responses to soluble proteins. Biochem. Biophys. Res. Commun. 1997, 240, 793–797. [CrossRef] [PubMed]
21. Miller, C.R.; Bondurant, B.; McLean, S.D.; McGovern, K.A.; O'Brien, D.F. Liposome_cell interactions in vitro: Effect of liposome surface charge on the binding and endocytosis of conventional and sterically stabilized liposomes. Biochemistry 1998, 37, 12875–12883. [CrossRef] [PubMed]
22. Foged, C.; Arigita, C.; Sundblad, A.; Jiskoot, W.; Storm, G.; Frokjaer, S. Interaction of dendritic cells with antigen-containing liposomes: Effect of bilayer composition. Vaccine 2004, 22, 1903–1913. [CrossRef] [PubMed]
23. Mazumdar, T.; Anam, K.; Ali, N. Influence of phospholipid composition on the adjuvanticity and protective efficacy of liposome-encapsulated leishmania donovani antigens. J. Parasitol. 2005, 91, 269–274. [CrossRef] [PubMed]
24. Badiee, A.; Jaafari, M.R.; Khamesipour, A.; Samiei, A.; Soroush, D.; Kheiri, M.T.; Barkhordari, F.; McMaster, W.R.; Mahboudi, F. Enhancement of immune response and protection in balb/c mice immunized with liposomal recombinant major surface glycoprotein of leishmania (rgp63): The role of bilayer composition. Colloids Surf. B 2009, 74, 37–44. [CrossRef] [PubMed]
25. Brunner, R.; Jensen-Jarolim, E.; Pali-Schöll, I. The abc of clinical and experimental adjuvants—A brief overview. Immunol. Lett. 2010, 128, 29–35. [CrossRef] [PubMed]
26. Brewer, J.M.; Tetley, L.; Richmond, J.; Liew, F.Y.; Alexander, J. Lipid vesicle size determines the th1 or th2 response to entrapped antigen. J. Immunol. 1998, 161, 4000–4007. [PubMed]
27. Oussoren, C.; Zuidema, J.; Crommelin, D.J.A.; Storm, G. Lymphatic uptake and biodistribution of liposomes after subcutaneous injection: Ii. Influence of liposomal size, lipid composition and lipid dose. Biochim. Biophys. Acta 1997, 1328, 261–272. [CrossRef]
28. Carstens, M.G.; Camps, M.G.M.; Henriksen-Lacey, M.; Franken, K.; Ottenhoff, T.H.M.; Perrie, Y.; Bouwstra, J.A.; Ossendorp, F.; Jiskoot, W. Effect of vesicle size on tissue localization and immunogenicity of liposomal DNA vaccines. Vaccine 2011, 29, 4761–4770. [CrossRef] [PubMed]
29. Henriksen-Lacey, M.; Christensen, D.; Bramwell, V.W.; Lindenstrøm, T.; Agger, E.M.; Andersen, P.; Perrie, Y. Liposomal cationic charge and antigen adsorption are important properties for the efficient deposition of antigen at the injection site and ability of the vaccine to induce a cmi response. J. Control. Release 2010, 145, 102–108. [CrossRef] [PubMed]
30. Kraaijeveld, C.A.; Schilham, M.; Jansen, J.; Benaissa-Trouw, B.; Harmsen, M.; van Houte, A.J.; Snippe, H. The effect of liposomal charge on the neutralizing antibody response against inactivated encephalomyocarditis and semliki forest viruses. Clin. Exp. Immunol. 1984, 56, 509–514. [PubMed]
31. Aggarwal, P.; Hall, J.B.; McLeland, C.B.; Dobrovolskaia, M.A.; McNeil, S.E. Nanoparticle interaction with plasma proteins as it relates to particle biodistribution, biocompatibility and therapeutic efficacy. Adv. Drug Deliv. Rev. 2009, 61, 428–437. [CrossRef] [PubMed]
32. Nel, A.E.; Madler, L.; Velegol, D.; Xia, T.; Hoek, E.M.V.; Somasundaran, P.; Klaessig, F.; Castranova, V.; Thompson, M. Understanding biophysicochemical interactions at the nano-bio interface. Nat. Mater. 2009, 8, 543–557. [CrossRef] [PubMed]
33. Owens D.E., III; Peppas, N.A. Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. Int. J. Pharm. 2006, 307, 93–102. [CrossRef] [PubMed]
34. Korsholm, K.S.; Petersen, R.V.; Agger, E.M.; Andersen, P. T-helper 1 and t-helper 2 adjuvants induce distinct differences in the magnitude, quality and kinetics of the early inflammatory response at the site of injection. Immunology 2010, 129, 75–86. [CrossRef] [PubMed]
35. Badiee, A.; Jaafari, M.R.; Khamesipour, A.; Samiei, A.; Soroush, D.; Kheiri, M.T.; Barkhordari, F.; McMaster, W.R.; Mahboudi, F. The role of liposome charge on immune response generated in balb/c mice immunized with recombinant major surface glycoprotein of leishmania (rgp63). Exp. Parasitol. 2009, 121, 362–369. [CrossRef] [PubMed]
36. Romberg, B.; Hennink, W.; Storm, G. Sheddable coatings for long-circulating nanoparticles. Pharm. Res. 2008, 25, 55–71. [CrossRef] [PubMed]
37. Li, Y.; Wang, J.; Gao, Y.; Zhu, J.; Wientjes, M.; Au, J. Relationships between liposome properties, cell membrane binding, intracellular processing, and intracellular bioavailability. AAPS J. 2011, 13, 585–597. [CrossRef] [PubMed]
38. Song, L.Y.; Ahkong, Q.F.; Rong, Q.; Wang, Z.; Ansell, S.; Hope, M.J.; Mui, B. Characterization of the inhibitory effect of peg-lipid conjugates on the intracellular delivery of plasmid and antisense DNA mediated by cationic lipid liposomes. Biochim. Biophys. Acta 2002, 1558, 1–13. [CrossRef]
39. Kaur, R.; Bramwell, V.W.; Kirby, D.J.; Perrie, Y. Manipulation of the surface pegylation in combination with reduced vesicle size of cationic liposomal adjuvants modifies their clearance kinetics from the injection site, and the rate and type of t cell response. J. Control. Release 2012. [CrossRef] [PubMed]
40. Kaur, R.; Bramwell, V.W.; Kirby, D.J.; Perrie, Y. Pegylation of dda:Tdb liposomal adjuvants reduces the vaccine depot effect and alters the th1/th2 immune responses. J. Control. Release 2012, 158, 72–77. [CrossRef] [PubMed]
41. Tanaka, Y.; Taneichi, M.; Kasai, M.; Kakiuchi, T.; Uchida, T. Liposome-coupled antigens are internalized by antigen-presenting cells via pinocytosis and cross-presented to cd8+ t cells. PLoS ONE 2010, 5, e15225. [CrossRef] [PubMed]
42. Christensen, D.; Henriksen-Lacey, M.; Kamath, A.T.; Lindenstrøm, T.; Korsholm, K.S.; Christensen, J.P.; Rochat, A.-F.; Lambert, P.-H.; Andersen, P.; Siegrist, C.-A. et al. A cationic vaccine adjuvant based on a saturated quaternary ammonium lipid have different in vivo distribution kinetics and display a distinct cd4 t cell-inducing capacity compared to its unsaturated analog. J. Control. Release 2012, 160, 468–476. [CrossRef] [PubMed]
43. Maisonneuve, C.; Bertholet, S.; Philpott, D.J.; De Gregorio, E. Unleashing the potential of nod- and toll-like agonists as vaccine adjuvants. Proc. Natl. Acad. Sci. USA 2014, 111, 12294–12299. [CrossRef] [PubMed]
44. Kaisho, T.; Akira, S. Toll-like receptor function and signaling. J. Allergy Clin. Immunol. 2006, 117, 979–987. [CrossRef] [PubMed]
45. Newton, K.; Dixit, V.M. Signaling in innate immunity and inflammation. Cold Spring Harb. Perspect. Biol. 2012. [CrossRef] [PubMed]
46. Geijtenbeek, T.B.H.; Gringhuis, S.I. Signalling through c-type lectin receptors: Shaping immune responses. Nat. Rev. Immunol. 2009, 9, 465–479. [CrossRef] [PubMed]
47. Agrawal, S.; Agrawal, A.; Doughty, B.; Gerwitz, A.; Blenis, J.; Van Dyke, T.; Pulendran, B. Cutting edge: Different toll-like receptor agonists instruct dendritic cells to induce distinct th responses via differential modulation of extracellular signal-regulated kinase-mitogen-activated protein kinase and c-fos. J. Immunol. 2003, 171, 4984–4989. [CrossRef] [PubMed]
48. Medzhitov, R. Toll-like receptors and innate immunity. Nat. Rev. Immunol. 2001, 1, 135–145. [CrossRef] [PubMed]
49. Jin, B.; Sun, T.; Yu, X.-H.; Liu, C.-Q.; Yang, Y.-X.; Lu, P.; Fu, S.-F.; Qiu, H.-B.; Yeo, A.E.T. Immunomodulatory effects of dsrna and its potential as vaccine adjuvant. J. Biomed. Biotechnol. 2010, 2010, 690438. [CrossRef] [PubMed]
50. Akira, S.; Uematsu, S.; Takeuchi, O. Pathogen recognition and innate immunity. Cell 2006, 124, 783–801. [CrossRef] [PubMed]
51. Bangham, A.D.; Standish, M.M.; Watkins, J.C. Diffusion of univalent ions across the lamellae of swollen phospholipids. J. Mol. Biol. 1965, 13, 238–IN227. [CrossRef]
52. Richards, R.L.; Rao, M.; Wassef, N.M.; Glenn, G.M.; Rothwell, S.W.; Alving, C.R. Liposomes containing lipid a serve as an adjuvant for induction of antibody and cytotoxic t-cell responses against rts,s malaria antigen. Infect. Immun. 1998, 66, 2859–2865. [PubMed]
53. Nordly, P.; Agger, E.; Andersen, P.; Nielsen, H.; Foged, C. Incorporation of the tlr4 agonist monophosphoryl lipid a into the bilayer of dda/tdb liposomes: Physico-chemical characterization and induction of cd8+ t-cell responses in vivo. Pharm. Res. 2011, 28, 553–562. [CrossRef] [PubMed]
54. Alving, C.R. Lipopolysaccharide, lipid a, and liposomes containing lipid a as immunologic adjuvants. Immunobiology 1993, 187, 430–446. [CrossRef]
55. Davidsen, J.; Rosenkrands, I.; Christensen, D.; Vangala, A.; Kirby, D.; Perrie, Y.; Agger, E.M.; Andersen, P. Characterization of cationic liposomes based on dimethyldioctadecylammonium and synthetic cord factor from m. Tuberculosis (trehalose 6,61-dibehenate)—A novel adjuvant inducing both strong cmi and antibody responses. Biochim. Biophys. Acta 2005, 1718, 22–31. [CrossRef] [PubMed]
56. Agger, E.M.; Rosenkrands, I.; Hansen, J.; Brahimi, K.; Vandahl, B.S.; Aagaard, C.; Werninghaus, K.; Kirschning, C.; Lang, R.; Christensen, D. et al. Cationic liposomes formulated with synthetic mycobacterial cordfactor (caf01): A versatile adjuvant for vaccines with different immunological requirements. PLoS ONE 2008, 3, e3116. [CrossRef] [PubMed]
57. Andersen, C.A.S.; Rosenkrands, I.; Olsen, A.W.; Nordly, P.; Christensen, D.; Lang, R.; Kirschning, C.; Gomes, J.M.; Bhowruth, V.; Minnikin, D.E. et al. Novel generation mycobacterial adjuvant based on liposome-encapsulated monomycoloyl glycerol from mycobacterium bovis bacillus calmette-guérin. J. Immunol. 2009, 183, 2294–2302. [CrossRef] [PubMed]
58. Andersen, C.S.; Agger, E.M.; Rosenkrands, I.; Gomes, J.M.; Bhowruth, V.; Gibson, K.J.C.; Petersen, R.V.; Minnikin, D.E.; Besra, G.S.; Andersen, P. A simple mycobacterial monomycolated glycerol lipid has potent immunostimulatory activity. J. Immunol. 2009, 182, 424–432. [CrossRef] [PubMed]
59. Nordly, P.; Korsholm, K.S.; Pedersen, E.A.; Khilji, T.S.; Franzyk, H.; Jorgensen, L.; Nielsen, H.M.; Agger, E.M.; Foged, C. Incorporation of a synthetic mycobacterial monomycoloyl glycerol analogue stabilizes dimethyldioctadecylammonium liposomes and potentiates their adjuvant effect in vivo. Eur. J. Pharm. Biopharm. 2011, 77, 89–98. [CrossRef] [PubMed]
60. Rosenkrands, I.; Vingsbo-Lundberg, C.; Bundgaard, T.J.; Lindenstrøm, T.; Enouf, V.; van der Werf, S.; Andersen, P.; Agger, E.M. Enhanced humoral and cell-mediated immune responses after immunization with trivalent influenza vaccine adjuvanted with cationic liposomes. Vaccine 2011, 29, 6283–6291. [CrossRef] [PubMed]
61. Copland, M.J.; Baird, M.A.; Rades, T.; McKenzie, J.L.; Becker, B.; Reck, F.; Tyler, P.C.; Davies, N.M. Liposomal delivery of antigen to human dendritic cells. Vaccine 2003, 21, 883–890. [CrossRef]
62. East, L.; Isacke, C.M. The mannose receptor family. Biochim. Biophys. Acta 2002, 1572, 364–386. [CrossRef]
63. Heurtault, B.; Gentine, P.; Thomann, J.-S.; Baehr, C.; Frisch, B.; Pons, F. Design of a liposomal candidate vaccine against pseudomonas aeruginosa and its evaluation in triggering systemic and lung mucosal immunity. Pharm. Res. 2009, 26, 276–285. [CrossRef] [PubMed]
64. Hanson, M.C.; Abraham, W.; Crespo, M.P.; Chen, S.H.; Liu, H.; Szeto, G.L.; Kim, M.; Reinherz, E.L.; Irvine, D.J. Liposomal vaccines incorporating molecular adjuvants and intrastructural t-cell help promote the immunogenicity of hiv membrane-proximal external region peptides. Vaccine 2015, 33, 861–868. [CrossRef] [PubMed]
65. Chen, W.; Huang, L. Induction of cytotoxic t-lymphocytes and antitumor activity by a liposomal lipopeptide vaccine. Mol. Pharm. 2008, 5, 464–471. [CrossRef] [PubMed]
66. Guan, H.H.; Budzynski, W.; Koganty, R.R.; Krantz, M.J.; Reddish, M.A.; Rogers, J.A.; Longenecker, B.M.; Samuel, J. Liposomal formulations of synthetic muc1 peptides: Effects of encapsulation versus surface display of peptides on immune responses. Bioconjug. Chem. 1998, 9, 451–458. [CrossRef] [PubMed]
67. Yuseff, M.-I.; Pierobon, P.; Reversat, A.; Lennon-Dumenil, A.-M. How b cells capture, process and present antigens: A crucial role for cell polarity. Nat. Rev. Immunol. 2013, 13, 475–486. [CrossRef] [PubMed]
68. Batista, F.D.; Harwood, N.E. The who, how and where of antigen presentation to b cells. Nat. Rev. Immunol. 2009, 9, 15–27. [CrossRef] [PubMed]
69. Shahum, E.; Thérien, H.-M. Liposomal adjuvanticity: Effect of encapsulation and surface-linkage on antibody production and proliferative response. Int. J. Immunopharmacol. 1995, 17, 9–20. [CrossRef]
70. Watson, D.S.; Huang, Z.; Szoka, F.C. All-trans retinoic acid potentiates the antibody response in mice to a lipopeptide antigen adjuvanted with liposomal lipid a. Immunol. Cell Biol. 2009, 87, 630–633. [CrossRef] [PubMed]
71. Fox, C.B.; Sivananthan, S.J.; Duthie, M.S.; Vergara, J.; Guderian, J.A.; Moon, E.; Coblentz, D.; Reed, S.G.; Carter, D. A nanoliposome delivery system to synergistically trigger tlr4 and tlr7. J. Nanobiotechnol. 2014, 12, 17. [CrossRef] [PubMed]
72. Jelinek, I.; Leonard, J.N.; Price, G.E.; Brown, K.N.; Meyer-Manlapat, A.; Goldsmith, P.K.; Wang, Y.; Venzon, D.; Epstein, S.L.; Segal, D.M. Tlr3-specific double-stranded rna oligonucleotide adjuvants induce dendritic cell cross-presentation, ctl responses, and antiviral protection. J. Immunol. 2011, 186, 2422–2429. [CrossRef] [PubMed]
73. Hafner, A.M.; Corthésy, B.; Merkle, H.P. Particulate formulations for the delivery of poly(i:C) as vaccine adjuvant. Adv. Drug Deliv. Rev. 2013, 65, 1386–1399. [CrossRef] [PubMed]
74. Klinman, D.M. Use of cpg oligodeoxynucleotides as immunoprotective agents. Expert Opin. Biol. Ther. 2004, 4, 937–946. [CrossRef] [PubMed]
75. Bode, C.; Zhao, G.; Steinhagen, F.; Kinjo, T.; Klinman, D.M. Cpg DNA as a vaccine adjuvant. Expert Rev. Vaccines 2011, 10, 499–511. [CrossRef] [PubMed]
76. Gursel, I.; Gursel, M.; Ishii, K.J.; Klinman, D.M. Sterically stabilized cationic liposomes improve the uptake and immunostimulatory activity of cpg oligonucleotides. J. Immunol. 2001, 167, 3324–3328. [CrossRef] [PubMed]
77. Ludewig, B.; Barchiesi, F.; Pericin, M.; Zinkernagel, R.M.; Hengartner, H.; Schwendener, R.A. In vivo antigen loading and activation of dendritic cells via a liposomal peptide vaccine mediates protective antiviral and anti-tumour immunity. Vaccine 2000, 19, 23–32. [CrossRef]
78. Andrews, C.D.; Huh, M.-S.; Patton, K.; Higgins, D.; Van Nest, G.; Ott, G.; Lee, K.-D. Encapsulating immunostimulatory cpg oligonucleotides in listeriolysin o-liposomes promotes a th1-type response and ctl activity. Mol. Pharm. 2012, 9, 1118–1125. [CrossRef] [PubMed]
79. Perrie, Y.; Gregoriadis, G. Liposome-entrapped plasmid DNA: Characterisation studies. Biochim. Biophys. Acta 2000, 1475, 125–132. [CrossRef]
80. Nordly, P.; Rose, F.; Christensen, D.; Nielsen, H.M.; Andersen, P.; Agger, E.M.; Foged, C. 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 2011, 150, 307–317. [CrossRef] [PubMed]
81. Shargh, V.H.; Jaafari, M.R.; Khamesipour, A.; Jaafari, I.; Jalali, S.A.; Abbasi, A.; Badiee, A. Liposomal sla co-incorporated with po cpg odns or ps cpg odns induce the same protection against the murine model of leishmaniasis. Vaccine 2012, 30, 3957–3964. [CrossRef] [PubMed]
82. Barnier-Quer, C.; Elsharkawy, A.; Romeijn, S.; Kros, A.; Jiskoot, W. Adjuvant effect of cationic liposomes for subunit influenza vaccine: Influence of antigen loading method, cholesterol and immune modulators. Pharmaceutics 2013, 5, 392–410. [CrossRef] [PubMed]
83. Hansen, J.; Lindenstrøm, T.; Lindberg-Levin, J.; Aagaard, C.; Andersen, P.; Agger, E. Caf05: Cationic liposomes that incorporate synthetic cord factor and poly(i:C) induce ctl immunity and reduce tumor burden in mice. Cancer Immunol. Immunother. 2011, 1–11. [CrossRef] [PubMed]
84. Korsholm, K.S.; Hansen, J.; Karlsen, K.; Filskov, J.; Mikkelsen, M.; Lindenstrøm, T.; Schmidt, S.T.; Andersen, P.; Christensen, D. Induction of cd8+ t-cell responses against subunit antigens by the novel cationic liposomal caf09 adjuvant. Vaccine 2014, 32, 3927–3935. [CrossRef] [PubMed]
85. Zaks, K.; Jordan, M.; Guth, A.; Sellins, K.; Kedl, R.; Izzo, A.; Bosio, C.; Dow, S. Efficient immunization and cross-priming by vaccine adjuvants containing tlr3 or tlr9 agonists complexed to cationic liposomes. J. Immunol. 2006, 176, 7335–7345. [CrossRef] [PubMed]
86. Mansourian, M.; Badiee, A.; Jalali, S.A.; Shariat, S.; Yazdani, M.; Amin, M.; Jaafari, M.R. Effective induction of anti-tumor immunity using p5 her-2/neu derived peptide encapsulated in fusogenic dotap cationic liposomes co-administrated with cpg-odn. Immunol. Lett. 2014, 162, 87–93. [CrossRef] [PubMed]
87. Varypataki, E.M.; van der Maaden, K.; Bouwstra, J.; Ossendorp, F.; Jiskoot,W. Cationic liposomes loaded with a synthetic long peptide and poly(i:C): A defined adjuvanted vaccine for induction of antigen-specific t cell cytotoxicity. AAPS J. 2015, 17, 216–226. [CrossRef] [PubMed]
88. Neeland, M.R.; Elhay, M.J.; Meeusen, E.N.T.; de Veer, M.J. Vaccination with liposomal poly(i:C) induces discordant maturation of migratory dendritic cell subsets and anti-viral gene signatures in afferent lymph cells. Vaccine 2014, 32, 6183–6192. [CrossRef] [PubMed]
89. Hemmi, H.; Kaisho, T.; Takeuchi, O.; Sato, S.; Sanjo, H.; Hoshino, K.; Horiuchi, T.; Tomizawa, H.; Takeda, K.; Akira, S. Small anti-viral compounds activate immune cells via the tlr7 myd88-dependent signaling pathway. Nat. Immunol. 2002, 3, 196–200. [CrossRef] [PubMed]
90. Grunwald, T.; Ulbert, S. Improvement of DNA vaccination by adjuvants and sophisticated delivery devices: Vaccine-platforms for the battle against infectious diseases. Clin. Exp. Vaccine Res. 2015, 4, 1–10. [CrossRef] [PubMed]
91. Gregoriadis, G.; Saffie, R.; de Souza, J.B. Liposome-mediated DNA vaccination. FEBS Lett. 1997, 402, 107–110. [CrossRef]
92. Perrie, Y.; Frederik, P.M.; Gregoriadis, G. Liposome-mediated DNA vaccination: The effect of vesicle composition. Vaccine 2001, 19, 3301–3310. [CrossRef]
93. Rodriguez, A.E.; Zamorano, P.; Wilkowsky, S.; Torrá, F.; Ferreri, L.; Dominguez, M.; Florin-Christensen, M. Delivery of recombinant vaccines against bovine herpesvirus type 1 gd and babesia bovis msa-2c to mice using liposomes derived from egg yolk lipids. Vet. J. 2013, 196, 550–551. [CrossRef] [PubMed]
94. Balbino, T.A.; Azzoni, A.R.; de la Torre, L.G. Microfluidic devices for continuous production of pdna/cationic liposome complexes for gene delivery and vaccine therapy. Colloids Surf. B 2013, 111, 203–210. [CrossRef] [PubMed]
95. Watson, D.S.; Endsley, A.N.; Huang, L. Design considerations for liposomal vaccines: Influence of formulation parameters on antibody and cell-mediated immune responses to liposome associated antigens. Vaccine 2012, 30, 2256–2272. [CrossRef] [PubMed]
96. Kedar, E.; Gur, H.; Babai, I.; Samira, S.; Even-Chen, S.; Barenholz, Y. Delivery of cytokines by liposomes: Hematopoietic and immunomodulatory activity of interleukin-2 encapsulated in conventional liposomes and in long-circulating liposomes. J. Immunother. 2000, 23, 131–145. [CrossRef] [PubMed]
97. Hamborg, M.; Jorgensen, L.; Bojsen, A.; Christensen, D.; Foged, C. Protein antigen adsorption to the dda/tdb liposomal adjuvant: Effect on protein structure, stability, and liposome physicochemical characteristics. Pharm. Res. 2013, 30, 140–155. [CrossRef] [PubMed]
98. Hamborg, M.; Rose, F.; Jorgensen, L.; Bjorklund, K.; Pedersen, H.B.; Christensen, D.; Foged, C. Elucidating the mechanisms of protein antigen adsorption to the caf/naf liposomal vaccine adjuvant systems: Effect of charge, fluidity and antigen-to-lipid ratio. Biochim. Biophys. Acta 2014, 1838, 2001–2010. [CrossRef] [PubMed]
99. Shek, P.N.; Heath, T.D. Immune response mediated by liposome-associated protein antigens. Iii. Immunogenicity of bovine serum albumin covalently coupled to vesicle surface. Immunology 1983, 50, 101–106. [PubMed]
100. Lockner, J.W.; Ho, S.O.; McCague, K.C.; Chiang, S.M.; Do, T.Q.; Fujii, G.; Janda, K.D. Enhancing nicotine vaccine immunogenicity with liposomes. Bioorg. Med. Chem. Lett. 2013, 23, 975–978. [CrossRef] [PubMed]
101. Faham, A.; Altin, J.G. Antigen-containing liposomes engrafted with flagellin-related peptides are effective vaccines that can induce potent antitumor immunity and immunotherapeutic effect. J. Immunol. 2010, 185, 1744–1754. [CrossRef] [PubMed]
102. Powers, D.C.; Hanscome, P.J.; Freda Pietrobon, P.J. In previously immunized elderly adults inactivated influenza a (h1n1) virus vaccines induce poor antibody responses that are not enhanced by liposome adjuvant. Vaccine 1995, 13, 1330–1335. [CrossRef]
103. Ambrosch, F.; Wiedermann, G.; Jonas, S.; Althaus, B.; Finkel, B.; Glück, R.; Herzog, C. Immunogenicity and protectivity of a new liposomal hepatitis a vaccine. Vaccine 1997, 15, 1209–1213. [CrossRef]
104. Childers, N.K.; Tong, G.; Mitchell, S.; Kirk, K.; Russell, M.W.; Michalek, S.M. A controlled clinical study of the effect of nasal immunization with a streptococcus mutans antigen alone or incorporated into liposomes on induction of immune responses. Infect. Immun. 1999, 67, 618–623. [PubMed]
105. Alvarez, M.J.; Echechipía, S.; García, B.; Tabar, A.I.; Martín, S.; Rico, P.; Olaguibel, J.M. Liposome-entrapped d. Pteronyssinus vaccination in mild asthma patients: Effect of 1-year double-blind, placebo-controlled trial on inflammation, bronchial hyper-responsiveness and immediate and late bronchial responses to the allergen. Clin. Exp. Allergy 2002, 32, 1574–1582. [CrossRef] [PubMed]
106. Ben-Yehuda, A.; Joseph, A.; Barenholz, Y.; Zeira, E.; Even-Chen, S.; Louria-Hayon, I.; Babai, I.; Zakay-Rones, Z.; Greenbaum, E.; Galprin, I. et al. Immunogenicity and safety of a novel il-2-supplemented liposomal influenza vaccine (influsome-vac) in nursing-home residents. Vaccine 2003, 21, 3169–3178. [CrossRef]
107. Ben-Yehuda, A.; Joseph, A.; Zeira, E.; Even-Chen, S.; Louria-Hayon, I.; Babai, I.; Zakay-Rones, Z.; Greenbaum, E.; Barenholz, Y.; Kedar, E. Immunogenicity and safety of a novel liposomal influenza subunit vaccine (influsome-vac) in young adults. J. Med. Virol. 2003, 69, 560–567. [CrossRef] [PubMed]
108. Lell, B.; Agnandji, S.; von Glasenapp, I.; Haertle, S.; Oyakhiromen, S.; Issifou, S.; Vekemans, J.; Leach, A.; Lievens, M.; Dubois, M.-C. et al. A randomized trial assessing the safety and immunogenicity of as01 and as02 adjuvanted rts,s malaria vaccine candidates in children in gabon. PLoS ONE 2009, 4, e7611. [CrossRef] [PubMed]
109. Kester, K.E.; Cummings, J.F.; Ofori-Anyinam, O.; Ockenhouse, C.F.; Krzych, U.; Moris, P.; Schwenk, R.; Nielsen, R.A.; Debebe, Z.; Pinelis, E. et al. Randomized, double-blind, phase 2a trial of falciparum malaria vaccines rts,s/as01b and rts,s/as02a in malaria-naive adults: Safety, efficacy, and immunologic associates of protection. J. Infect. Dis. 2009, 200, 337–346. [CrossRef] [PubMed]
110. Polhemus, M.E.; Remich, S.A.; Ogutu, B.R.; Waitumbi, J.N.; Otieno, L.; Apollo, S.; Cummings, J.F.; Kester, K.E.; Ockenhouse, C.F.; Stewart, A. et al. Evaluation of rts,s/as02a and rts,s/as01b in adults in a high malaria transmission area. PLoS ONE 2009, 4, e6465. [CrossRef] [PubMed]
111. Wu, Y.-L.; Park, K.; Soo, R.A.; Sun, Y.; Tyroller, K.; Wages, D.; Ely, G.; Yang, J.C.-H.; Mok, T. Inspire: A phase iii study of the blp25 liposome vaccine (l-blp25) in asian patients with unresectable stage iii non-small cell lung cancer. BMC Cancer 2011, 11, 430–430. [CrossRef] [PubMed]
112. Zollinger, W.D.; Babcock, J.G.; Moran, E.E.; Brandt, B.L.; Matyas, G.R.; Wassef, N.M.; Alving, C.R. Phase i study of a neisseria meningitidis liposomal vaccine containing purified outer membrane proteins and detoxified lipooligosaccharide. Vaccine 2012, 30, 712–721. [CrossRef] [PubMed]
113. Hamilton, E.; Blackwell, K.; Hobeika, A.C.; Clay, T.M.; Broadwater, G.; Ren, X.-R.; Chen, W.; Castro, H.; Lehmann, F.; Spector, N. et al. Phase i clinical trial of her2-specific immunotherapy with concomitant her2 kinase inhibtion. J. Transl. Med. 2012, 10, 28–28. [CrossRef] [PubMed]
114. Román, V.R.G.; Jensen, K.J.; Jensen, S.S.; Leo-Hansen, C.; Jespersen, S.; Té, D.D.S.; Rodrigues, C.M.; Janitzek, C.M.; Vinner, L.; Katzenstein, T.L. et al. Therapeutic vaccination using cationic liposome-adjuvanted hiv type 1 peptides representing hla-supertype-restricted subdominant t cell epitopes: Safety, immunogenicity, and feasibility in guinea-bissau. AIDS Res. Hum. Retrovir. 2013, 29, 1504–1512. [CrossRef] [PubMed]
115. Montoya, J.; Solon, J.A.; Cunanan, S.R.C.; Acosta, L.; Bollaerts, A.; Moris, P.; Janssens, M.; Jongert, E.; Demoitié, M.-A.; Mettens, P. et al. A randomized, controlled dose-finding phase ii study of the m72/as01 candidate tuberculosis vaccine in healthy ppd-positive adults. J. Clin. Immunol. 2013, 33, 1360–1375. [CrossRef] [PubMed]
116. van Dissel, J.T.; Joosten, S.A.; Hoff, S.T.; Soonawala, D.; Prins, C.; Hokey, D.A.; O’Dee, D.M.; Graves, A.; Thierry-Carstensen, B.; Andreasen, L.V. et al. A novel liposomal adjuvant system, caf01, promotes long-lived mycobacterium tuberculosis-specific t-cell responses in human. Vaccine 2014, 32, 7098–7107. [CrossRef] [PubMed]
117. Marty-Roix, R.; Vladimer, G.I.; Pouliot, K.; Weng, D.; Buglione-Corbett, R.; West, K.; MacMicking, J.D.; Chee, J.D.; Wang, S.; Lu, S. et al. Identification of qs-21 as an inflammasome-activating molecular component of saponin adjuvants. J. Biol. Chem. 2015, 291, 1123–1136. [CrossRef] [PubMed]
118. Merck KGAA. Merck discontinues clinical development program of tecemotide as a monotherapy in stage iii non-small cell lung cancer. http://www.merckgroup.com/en/media/ extNewsDetail.html?newsId=8475BA17A3F51470C1257D50006901B4&newsType=1 (accessed on 16 November 2015).
119. De Gregorio, E.; Rappuoli, R. From empiricism to rational design: A personal perspective of the evolution of vaccine development. Nat. Rev. Immunol. 2014, 14, 505–514. [CrossRef] [PubMed]