The role of bacterial lipopolysaccharides as immune modulator in vaccine and drug development

Endocrine, Metabolic and Immune Disorders - Drug Targets

Volumn 12, Issue 3, 2012, Pages 221-235

  Arenas, Jesús ^a  

^a UTRECHT UNIVERSITY   (Netherlands)

Author keywords

Adjuvant; Bacterial LPS; Drug development; Immune disorders

Indexed keywords

2 DEOXY 3 O (9 PHENYLNONANOYL) 2 [3 (9 PHENYLNONANOYLOXY)TETRADECANOYLAMINO]GLUCOPYRANOSE 4 SULFATE; BACTERIUM LIPOPOLYSACCHARIDE; CRX 526; E 6020; ERITORAN; HEPATITIS B VACCINE; IMMUNOMODULATING AGENT; LIPID A DERIVATIVE; MIFAMURTIDE; PHOSPHORYL LIPID A; RC 529; UNCLASSIFIED DRUG; WART VIRUS VACCINE;

ACINETOBACTER BAUMANNII; ADJUVANT THERAPY; AUTOIMMUNE DISEASE; BORDETELLA; BORDETELLA PERTUSSIS; CAMPYLOBACTER; CLONAL ANERGY; CYANOBACTERIUM; DRUG ACTIVITY; DRUG DELIVERY SYSTEM; DRUG MECHANISM; DRUG MEGADOSE; DRUG SYNTHESIS; ENDOTOXEMIA; ENTERITIS; ESCHERICHIA COLI; HAEMOPHILUS; HALOMONAS; HUMAN; IMMUNOSTIMULATION; IMMUNOTHERAPY; IN VITRO STUDY; INSULIN DEPENDENT DIABETES MELLITUS; MORAXELLA CATARRHALIS; NEISSERIA GONORRHOEAE; NEISSERIA MENINGITIDIS; NONHUMAN; PANTOEA AGGLOMERANS; REVIEW; RHODOBACTER CAPSULATUS; RHODOBACTER SPHAEROIDES; SALMONELLA; SEPSIS; SEPTIC SHOCK; WHOLE CELL;

ANIMALS; DRUG DESIGN; HUMANS; IMMUNE SYSTEM DISEASES; IMMUNOLOGIC FACTORS; IMMUNOSUPPRESSIVE AGENTS; IMMUNOTHERAPY; LIPOPOLYSACCHARIDES; SEPSIS; VACCINES;

EID: 84864771000     PISSN: 18715303     EISSN: 22123873     Source Type: Journal    
DOI: 10.2174/187153012802002884     Document Type: Review

References (195)

1. Kumar, H.; Kawai, T. and Akira, S. (2009) Pathogen recognition in the innate immune response. Biochem. J., 420, 1-16.
2. Kawai, T. and Akira, S. (2011) Toll-like receptors and their crosstalk with other innate receptors in infection and immunity. Immunity, 34, 637-650.
3. Osorio, F. and Reise Sousa, C. (2011) Myeloid C-type lectin receptors in pathogen recognition and host defense. Immunity, 34, 651-664.
4. Palsson-McDermott, E.M. and O'Neill, L.A. (2004) Signal transduction by the lipopolysaccharide receptor, Toll-like receptor-4. Immunology, 113, 153-162.
5. Trinchieri, G. and Sher, A. (2007) Cooperation of Toll-like receptor signals in innate immune defence. Nat. Rev. Immunol., 7, 179-190.
6. Kawai, T. and Akira, S. (2006) TLR signaling. Cell Death. Differ., 13, 816-825.
7. Miggin, S.M. and O'Neill, L.A. (2006) New insights into the regulation of TLR signaling. J. Leukoc. Biol., 80, 220-226.
8. Alexander, C. and Rietschel, E.T. (2001) Bacterial lipopolysaccharides and innate immunity. J. Endotoxin. Res., 7, 167-202.
9. Kotani, S. and Takada, H. (1990) Structural requirements of lipid A for endotoxicity and other biological activities--an overview. Adv. Exp. Med. Biol., 256, 13-43.
10. Nowotny, A. (1969) Molecular aspects of endotoxic reactions. Bacteriol. Rev., 33, 72-98.
11. Conti, P.; Dempsey, R.A.; Reale, M.; Barbacane, R.C.; Panara, M.R.; Bongrazio, M. and Mier, J.W. (1991) Activation of human natural killer cells by lipopolysaccharide and generation of interleukin-1 alpha, beta, tumour necrosis factor and interleukin-6. Effect of IL-1 receptor antagonist. Immunology, 73, 450-456.
12. Kobayashi, M.; Fitz, L.; Ryan, M.; Hewick, R.M.; Clark, S.C.; Chan, S.; Loudon, R.; Sherman, F.; Perussia, B. and Trinchieri, G. (1989) Identification and purification of natural killer cell stimulatory factor (NKSF), a cytokine with multiple biologic effects on human lymphocytes. J. Exp. Med., 170, 827-845.
13. Morrison, D.C. and Kline, L.F. (1977) Activation of the classical and properdin pathways of complement by bacterial lipopolysaccharides (LPS). J. Immunol., 118, 362-368.
14. Cooper, N.R. and Morrison, D.C. (1978) Binding and activation of the first component of human complement by the lipid A region of lipopolysaccharides. J. Immunol., 120, 1862-1868.
15. Soghoian, D.Z. and Streeck, H. (2010) Cytolytic CD4(+) T cells in viral immunity. Expert. Rev. Vaccines, 9, 1453-1463.
16. Galon, J.; Costes, A.; Sanchez-Cabo, F.; Kirilovsky, A.; Mlecnik, B.; Lagorce-Pages, C.; Tosolini, M.; Camus, M.; Berger, A.; Wind, P.; Zinzindohoué, F.; Bruneval, P.; Cugnenc, P.H.; Trajanoski, Z.; Fridman, W.H. and Pagès, F. (2006) Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science, 313, 1960-1964.
17. Pages, F.; Berger, A.; Camus, M.; Sanchez-Cabo, F.; Costes, A.; Molidor, R.; Mlecnik, B.; Kirilovsky, A.; Nilsson, M.; Damotte, D.; Meatchi, T.; Bruneval, P.; Cugnenc, P.H.; Trajanoski, Z.; Fridman, W.H. and Galon, J. (2005) Effector memory T cells, early metastasis, and survival in colorectal cancer. N. Engl. J. Med., 353, 2654-2666.
18. Cinel, I. and Dellinger, R.P. (2007) Advances in pathogenesis and management of sepsis. Curr. Opin. Infect. Dis., 20, 345-352.
19. Annane, D.; Bellissant, E. and Cavaillon, J.M. (2005) Septic shock. Lancet, 365, 63-78.
20. Vincent, J.L.; Sakr, Y.; Sprung, C.L.; Ranieri, V.M.; Reinhart, K.; Gerlach, H.; Moreno, R.; Carlet, J.; Le Gall, J.R. and Payen, D. (2006) Sepsis in European intensive care units: results of the SOAP study. Crit. Care Med., 34, 344-353.
21. Martin, G.S.; Mannino, D.M.; Eaton, S. and Moss, M. (2003) The epidemiology of sepsis in the United States from 1979 through 2000. N. Engl. J. Med., 348, 1546-1554.
22. Rietschel, E.T.; Schade, U.; Jensen, M.; Wollenweber, H.W.; Luderitz, O. and Greisman, S.G. (1982) Bacterial endotoxins: chemical structure, biological activity and role in septicaemia. Scand. J. Infect. Dis. Suppl., 31, 8-21.
23. Preston, A.; Mandrell, R.E.; Gibson, B.W. and Apicella, M.A. (1996) The lipooligosaccharides of pathogenic gram-negative bacteria. Crit. Rev. Microbiol., 22, 139-180.
24. Golenbock, D.T.; Hampton, R.Y.; Qureshi, N.; Takayama, K. and Raetz, C.R. (1991) Lipid A-like molecules that antagonize the effects of endotoxins on human monocytes. J. Biol. Chem., 266, 19490-19498.
25. Kotani, S.; Takada, H.; Tsujimoto, M.; Ogawa, T.; Takahashi, I.; Ikeda, T.; et al. (1985) Synthetic lipid A with endotoxic and related biological activities comparable to those of a natural lipid A from an Escherichia coli re-mutant. Infect. Immun., 49, 225-237.
26. Miller, S.I.; Ernst, R.K. and Bader, M.W. (2005) LPS, TLR4 and infectious disease diversity. Nat. Rev. Microbiol., 3, 36-46.
27. van Deuren, M.; Brandtzaeg, P. and van der Meer, J.W. (2000) Update on meningococcal disease with emphasis on pathogenesis and clinical management. Clin. Microbiol. Rev., 13, 144-166.
28. Hynes, S.O.; Ferris, J.A.; Szponar, B.; Wadstrom, T.; Fox, J.G.; O'Rourke, J.; Larsson, L.; Yaquian, E.; Ljungh, A.; Clyne, M.; Andersen, L.P. and Moran, A.P. (2004) Comparative chemical and biological characterization of the lipopolysaccharides of gastric and enterohepatic helicobacters. Helicobacter, 9, 313-323.
29. Perez-Perez, G.I.; Shepherd, V.L.; Morrow, J.D. and Blaser, M.J. (1995) Activation of human THP-1 cells and rat bone marrowderived macrophages by Helicobacter pylori lipopolysaccharide. Infect. Immun., 63, 1183-1187.
30. Saitoh, S.; Akashi, S.; Yamada, T.; Tanimura, N.; Kobayashi, M.; Konno, K.; Fukase, K.; Kusumoto, S.; Nagai, Y.; Kusumoto, Y.; Kosugi, A. and Miyake, K. (2004) Lipid A antagonist, lipid IVa, is distinct from lipid A in interaction with Toll-like receptor 4 (TLR4)-MD-2 and ligand-induced TLR4 oligomerization. Int. Immunol., 16, 961-969.
31. Raetz, C.R. and Whitfield, C. (2002) Lipopolysaccharide endotoxins. Annu. Rev. Biochem., 71, 635-700.
32. Salimath, P.V.; Weckesser, J.; Strittmatter, W. and Mayer, H. (1983) Structural studies on the non-toxic lipid A from Rhodopseudomonas sphaeroides ATCC 17023. Eur. J. Biochem., 136, 195-200.
33. Salimath, P.V.; Tharanathan, R.N.; Weckesser, J. and Mayer, H. (1984) The structure of the polysaccharide moiety of Rhodopseudomonas sphaeroides ATCC 17023 lipopolysaccharide. Eur. J. Biochem., 144, 227-232.
34. Loppnow, H.; Libby, P.; Freudenberg, M.; Krauss, J.H.; Weckesser, J. and Mayer, H. (1990) Cytokine induction by lipopolysaccharide (LPS) corresponds to lethal toxicity and is inhibited by nontoxic Rhodobacter capsulatus LPS. Infect. Immun., 58, 3743-3750.
35. Krauss, J.H.; Seydel, U.; Weckesser, J. and Mayer, H. (1989) Structural analysis of the nontoxic lipid A of Rhodobacter capsulatus 37b4. Eur. J. Biochem., 180, 519-526.
36. Jemmett, K.; Macagno, A.; Molteni, M.; Heckels, J.E.; Rossetti, C. and Christodoulides, M. (2008) A cyanobacterial lipopolysaccharide antagonist inhibits cytokine production induced by Neisseria meningitidis in a human whole-blood model of septicemia. Infect. Immun., 76, 3156-3163.
37. Ialenti, A.; Di, M.P.; Grassia, G.; Maffia, P.; Di, R.M.; Lanzetta, R.; Molinaro, A.; Silipo, A.; Grant, W. and Ianaro, A. (2006) A novel lipid A from Halomonas magadiensis inhibits enteric LPS-induced human monocyte activation. Eur. J. Immunol., 36, 354-360.
38. Zughaier, S.M.; Tzeng, Y.L.; Zimmer, S.M.; Datta, A.; Carlson, R.W. and Stephens, D.S. (2004) Neisseria meningitidis lipooligosaccharide structure-dependent activation of the macrophage CD14/Toll-like receptor 4 pathway. Infect. Immun., 72, 371-380.
39. Geurtsen, J.; Dzieciatkowska, M.; Steeghs, L.; Hamstra, H.J.; Boleij, J.; Broen, K.; Akkerman, G.; El Hassan, H.; Li, J.; Richards, J.C.; Tommassen, J. and van der Ley, P. (2009) Identification of a novel lipopolysaccharide core biosynthesis gene cluster in Bordetella pertussis, and influence of core structure and lipid A glucosamine substitution on endotoxic activity. Infect. Immun., 77, 2602-2611.
40. Gringhuis, S.I.; den Dunnen, J.; Litjens, M.; van Het Hof, B.; van Kooyk, Y. and Geijtenbeek, T.B. (2007) C-type lectin DC-SIGN modulates Toll-like receptor signaling via Raf-1 kinase-dependent acetylation of transcription factor NF-kappaB. Immunity, 26, 605-616.
41. Apicella, M.A.; Shero, M.; Jarvis, G.A.; Griffiss, J.M.; Mandrell, R.E. and Schneider, H. (1987) Phenotypic variation in epitope expression of the Neisseria gonorrhoeae lipooligosaccharide. Infect. Immun., 55, 1755-1761.
42. Danaher, R.J.; Levin, J.C.; Arking, D.; Burch, C.L.; Sandlin, R. and Stein, D.C. (1995) Genetic basis of Neisseria gonorrhoeae lipooligosaccharide antigenic variation. J. Bacteriol., 177, 7275-7279.
43. van Vliet, S.J.; Steeghs, L.; Bruijns, S.C.; Vaezirad, M.M.; Snijders, B.C.; Arenas Busto, J.A.; Deken, M.; van Putten, J.P. and van Kooyk, Y. (2009) Variation of Neisseria gonorrhoeae lipooligosaccharide directs dendritic cell-induced T helper responses. PLoS. Pathog, 5, e1000625.
44. Geurtsen, J.; Steeghs, L.; Hamstra, H.J.; Ten Hove, J.; de Haan, A.; Kuipers, B.; Tommassen, J. and van der Ley, P. (2006) Expression of the lipopolysaccharide-modifying enzymes PagP and PagL modulates the endotoxic activity of Bordetella pertussis. Infect. Immun., 74, 5574-5585.
45. Geurtsen, J.; Vandebriel, R.J.; Gremmer, E.R.; Kuipers, B.; Tommassen, J. and van der Ley, P. (2007) Consequences of the expression of lipopolysaccharide-modifying enzymes for the efficacy and reactogenicity of whole-cell pertussis vaccines. Microbes. Infect., 9, 1096-1103.
46. Steeghs, L.; Berns, M.; Ten Hove, J.; de Jong, A.; Roholl, P.; van Alphen, L.; Tommassen, J. and van der Ley, P. (2002) Expression of foreign LpxA acyltransferases in Neisseria meningitidis results in modified lipid A with reduced toxicity and retained adjuvant activity. Cell Microbiol., 4, 599-611.
47. Doerrler, W.T.; Gibbons, H.S. and Raetz, C.R. (2004) MsbAdependent translocation of lipids across the inner membrane of Escherichia coli. J. Biol. Chem., 279, 45102-45109.
48. Zhou, Z.; White, K.A.; Polissi, A.; Georgopoulos, C. and Raetz, C.R. (1998) Function of Escherichia coli MsbA, an essential ABC family transporter, in lipid A and phospholipid biosynthesis. J. Biol. Chem., 273, 12466-12475.
49. Bowyer, A.; Baardsnes, J.; Ajamian, E.; Zhang, L. and Cygler, M. (2011) Characterization of interactions between LPS transport proteins of the Lpt system. Biochem. Biophys. Res. Commun., 404, 1093-1098.
50. Silhavy, T.J.; Kahne, D. and Walker, S. (2010) The bacterial cell envelope. Cold Spring Harb. Perspect. Biol, 2, a000414.
51. Wu, T.; McCandlish, A.C.; Gronenberg, L.S.; Chng, S.S.; Silhavy, T.J. and Kahne, D. (2006) Identification of a protein complex that assembles lipopolysaccharide in the outer membrane of Escherichia coli. Proc. Natl. Acad. Sci. USA, 103, 11754-11759.
52. Steeghs, L.; den Hartog, R.; den Boer, A.; Zomer, B.; Roholl, P. and van der Ley, P. (1998) Meningitis bacterium is viable without endotoxin. Nature, 392, 449-450.
53. Moffatt, J.H.; Harper, M.; Harrison, P.; Hale, J.D.; Vinogradov, E.; Seemann, T.; Henry, R.; Crane, B.; St Michael, F.; Cox, A.D.; Adler, B.; Nation, R.L.; Li, J. and Boyce, J.D. (2010) Colistin resistance in Acinetobacter baumannii is mediated by complete loss of lipopolysaccharide production. Antimicrob. Agents Chemother., 54, 4971-4977.
54. Guo, L.; Lim, K.B.; Poduje, C.M.; Daniel, M.; Gunn, J.S.; Hackett, M.; Miller, S.I. (1998) Lipid A acylation and bacterial resistance against vertebrate antimicrobial peptides. Cell, 95, 189-198.
55. Gibbons, H.S.; Lin, S.; Cotter, R.J. and Raetz, C.R. (2000) Oxygen requirement for the biosynthesis of the S-2-hydroxymyristate moiety in Salmonella typhimurium lipid A. Function of LpxO, A new Fe2+/alpha-ketoglutarate-dependent dioxygenase homologue. J. Biol. Chem., 275, 32940-32949.
56. Reynolds, C.M.; Ribeiro, A.A.; McGrath, S.C.; Cotter, R.J.; Raetz, C.R. and Trent, M.S. (2006) An outer membrane enzyme encoded by Salmonella typhimurium lpxR that removes the 3'-acyloxyacyl moiety of lipid A. J. Biol. Chem., 281, 21974-21987.
57. Trent, M.S.; Pabich, W.; Raetz, C.R. and Miller, S.I. (2001) A PhoP/PhoQ-induced Lipase (PagL) that catalyzes 3-O-deacylation of lipid A precursors in membranes of Salmonella typhimurium. J. Biol. Chem., 276, 9083-9092.
58. Guo, L.; Lim, K.B.; Gunn, J.S.; Bainbridge, B.; Darveau, R.P.; Hackett, M. and Miller, S.I. (1997) Regulation of lipid A modifications by Salmonella typhimurium virulence genes phoPphoQ. Science, 276, 250-253.
59. Trent, M.S.; Stead, C.M.; Tran, A.X. and Hankins, J.V. (2006) Diversity of endotoxin and its impact on pathogenesis. J. Endotoxin. Res., 12, 205-223.
60. Brito, L.A. and Singh, M. (2011) Acceptable levels of endotoxin in vaccine formulations during preclinical research. J. Pharm. Sci., 100, 34-37.
61. van Putten, J.P.; Bouwman, L.I. and de Zoete, M.R. (2010) Unraveling bacterial interactions with toll-like receptors. Immunol. Lett., 128, 8-11.
62. David, S.; Vermeer-de Bondt, P.E. and van der Maas, N.A. (2008) Reactogenicity of infant whole cell pertussis combination vaccine compared with acellular pertussis vaccines with or without simultaneous pneumococcal vaccine in the Netherlands. Vaccine, 26, 5883-5887.
63. Gustafsson, L.; Hallander, H.O.; Olin, P.; Reizenstein, E. and Storsaeter, J. (1996) A controlled trial of a two-component acellular, a five-component acellular, and a whole-cell pertussis vaccine. N. Engl. J. Med., 334, 349-355.
64. Martich, G.D.; Boujoukos, A.J. and Suffredini, A.F. (1993) Response of man to endotoxin. Immunobiology, 187, 403-416.
65. Copeland, S.; Warren, H.S.; Lowry, S.F.; Calvano, S.E. and Remick, D. (2005) Acute inflammatory response to endotoxin in mice and humans. Clin. Diagn. Lab Immunol., 12, 60-67.
66. van der Ley, P. and van den Dobbelsteen, G. (2011) Nextgeneration outer membrane vesicle vaccines against Neisseria meningitidis based on nontoxic LPS mutants. Hum. Vaccin., 7, 886-890.
67. Dey, A.K. and Srivastava, I.K. (2011) Novel adjuvants and delivery systems for enhancing immune responses induced by immunogens. Expert. Rev. Vaccines, 10, 227-251.
68. Nicholls, E.F.; Madera, L. and Hancock, R.E. (2010) Immunomodulators as adjuvants for vaccines and antimicrobial therapy. Ann. N. Y. Acad. Sci., 1213, 46-61.
69. Dubensky, T.W. Jr. and Reed, S.G. (2010) Adjuvants for cancer vaccines. Semin. Immunol., 22, 155-161.
70. Ziegler, A.; Heidenreich, R.; Braumuller, H.; Wolburg, H.; Weidemann, S.; Mocikat, R. and Röcken M. (2009) EpCAM, a human tumor-associated antigen promotes Th2 development and tumor immune evasion. Blood, 113, 3494-3502.
71. Curiel, T.J.; Coukos, G.; Zou, L.; Alvarez, X.; Cheng, P.; Mottram, P.; Evdemon-Hogan, M.; Conejo-Garcia, J.R.; Zhang, L.; Burow, M.; Zhu, Y.; Wei, S.; Kryczek, I.; Daniel, B.; Gordon, A.; Myers, L.; Lackner, A.; Disis, M.L.; Knutson, K.L.; Chen, L. and Zou, W. (2004) Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat. Med., 10, 942-949.
72. Lambrecht, B.N.; Kool, M.; Willart, M.A. and Hammad, H. (2009) Mechanism of action of clinically approved adjuvants. Curr. Opin. Immunol., 21, 23-29.
73. Sharp, F.A.; Ruane, D.; Claass, B.; Creagh, E.; Harris, J.; Malyala, P.; Singh, M.; O'Hagan, D.T.; Pétrilli, V.; Tschopp, J.; O'Neill, L.A. and Lavelle, E.C. (2009) Uptake of particulate vaccine adjuvants by dendritic cells activates the NALP3 inflammasome. Proc. Natl. Acad. Sci. USA, 106, 870-875.
74. Brewer, J.M.; Conacher, M.; Hunter, C.A.; Mohrs, M.; Brombacher, F. and Alexander, J. (1999) Aluminium hydroxide adjuvant initiates strong antigen-specific Th2 responses in the absence of IL-4-or IL-13-mediated signaling. J. Immunol., 163, 6448-6454.
75. Fox, C.B. (2009) Squalene emulsions for parenteral vaccine and drug delivery. Molecules, 14, 3286-3312.
76. O'Hagan, D.T. (2007) MF59 is a safe and potent vaccine adjuvant that enhances protection against influenza virus infection. Expert. Rev. Vaccines, 6, 699-710.
77. Scheifele, D.W.; Ward, B.J.; Dionne, M.; Vanderkooi, O.; Langley, J.M.; Dobson, S.; Li, Y.; Law, B. and Halperin, S.A. (2011) Evaluation of adjuvanted pandemic H1N1(2009) influenza vaccine after one and two doses in young children. Pediatr. Infect. Dis. J., 30, 402-407.
78. Coler, R.N.; Carter, D.; Friede, M. and Reed, S.G. (2009) Adjuvants for malaria vaccines. Parasite Immunol., 31, 520-528.
79. Leroux-Roels, G. (2010) Unmet needs in modern vaccinology: adjuvants to improve the immune response. Vaccine, 28(Suppl 3), C25-C36.
80. Ostrowski, M.A.; Yu, Q.; Yue, F.Y.; Liu, J.; Jones, B.; Gu, X.X.; Loutfy, M.; Kovacs, C.M. and Halpenny, R. (2006) Why can't the immune system control HIV-1? Defining HIV-1-specific CD4+ T cell immunity in order to develop strategies to enhance viral immunity. Immunol. Res., 35, 89-102.
81. Dasilva, K.A.; Aubert, I. and McLaurin, J. (2006) Vaccine development for Alzheimer's disease. Curr. Pharm. Des., 12, 4283-4293.
82. Sela, M. (2006) Immunomodulatory vaccines against autoimmune diseases. Rejuvenation Res., 9, 126-133.
83. Zepp, F. (2010) Principles of vaccine design-Lessons from nature. Vaccine, 28(Suppl 3), C14-C24.
84. Garcon, N.; Chomez, P. and Van Mechelen, M. (2007) GlaxoSmithKline Adjuvant Systems in vaccines: concepts, achievements and perspectives. Expert. Rev. Vaccines., 6, 723-739.
85. Casella, C.R. and Mitchell, T.C. (2008) Putting endotoxin to work for us: monophosphoryl lipid A as a safe and effective vaccine adjuvant. Cell Mol. Life Sci., 65, 3231-3240.
86. Fox, C.B.; Friede, M.; Reed, S.G. and Ireton, G.C. (2010) Synthetic and natural TLR4 agonists as safe and effective vaccine adjuvants. Subcell. Biochem., 53, 303-321.
87. Ribi, E.; Parker, R.; Strain, S.M.; Mizuno, Y.; Nowotny, A.; von Eschen, K.B.; Cantrell, J.L.; McLaughlin, C.A.; Hwang, K.M.; Goren, M.B. (1979) Peptides as requirement for immuno therapy of the guinea-pig line-10 tumor with endotoxins. Cancer Immunol. Immunother., 7, 43-58.
88. Baldridge, J.R. and Crane, R.T. (1999) Monophosphoryl lipid A (MPL) formulations for the next generation of vaccines. Methods, 19, 103-107.
89. Evans, J.T.; Cluff, C.W.; Johnson, D.A.; Lacy, M.J.; Persing, D.H. and Baldridge, J.R. (2003) Enhancement of antigen-specific immunity via the TLR4 ligands MPL adjuvant and Ribi.529. Expert. Rev. Vaccines., 2, 219-229.
90. Yamamoto, M.; Sato, S.; Hemmi, H.; Hoshino, K.; Kaisho, T.; Sanjo, H.; Takeuchi, O.; Sugiyama, M.; Okabe, M.; Takeda, K. and Akira, S. (2003) Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway. Science, 301, 640-643.
91. Hirotani, T.; Yamamoto, M.; Kumagai, Y.; Uematsu, S.; Kawase, I.; Takeuchi, O.; Akira, S. (2005) Regulation of lipopolysaccharide-inducible genes by MyD88 and Toll/IL-1 domain containing adaptor inducing IFN-beta. Biochem. Biophys. Res. Commun., 328, 383-392.
92. O'Neill, L.A. and Bowie, A.G. (2007) The family of five: TIRdomain-containing adaptors in Toll-like receptor signalling. Nat. Rev. Immunol., 7, 353-364.
93. Mata-Haro, V.; Cekic, C.; Martin, M.; Chilton, P.M.; Casella, C.R. and Mitchell, T.C. (2007) The vaccine adjuvant monophosphoryl lipid A as a TRIF-biased agonist of TLR4. Science, 316, 1628-1632.
94. Ulrich, J.T. and Myers, K.R. (1995) Monophosphoryl lipid A as an adjuvant. Past experiences and new directions. Pharm. Biotechnol., 6, 495-524.
95. Vajdy, M. and Singh, M. (2005) The role of adjuvants in the development of mucosal vaccines. Expert. Opin. Biol. Ther., 5, 953-965.
96. Kidon, M.I.; Shechter, E. and Toubi, E. (2011) [Vaccination against human papilloma virus and cervical cancer]. Harefuah, 150, 33-6, 68.
97. Labadie, J. (2011) Postlicensure safety evaluation of human papilloma virus vaccines. Int. J. Risk Saf. Med., 23, 103-112.
98. Kundi, M. (2007) New hepatitis B vaccine formulated with an improved adjuvant system. Expert. Rev. Vaccines, 6, 133-140.
99. Aide, P.; Dobano, C.; Sacarlal, J.; Aponte, J.J.; Mandomando, I.; Guinovart, C.; Bassat, Q.; Renom, M.; Puyol, L.; Macete, E.; Herreros, E.; Leach, A.; Dubois, M.C.; Demoitie, M.A.; Lievens, M.; Vekemans, J.; Loucq, C.; Ballou, W.R.; Cohen, J. and Alonso, P.L. (2011) Four year immunogenicity of the RTS, S/AS02(A) malaria vaccine in Mozambican children during a phase IIb trial. Vaccine, 29, 6059-6067.
100. Von Eschen, K.; Morrison, R.; Braun, M.; Ofori-Anyinam, O.; De Kock, E.; Pavithran, P.; Koutsoukos, M.; Moris, P.; Cain, D.; Dubois, M.C.; Cohen, J. and Ballou, W.R. (2009) The candidate tuberculosis vaccine Mtb72F/AS02A: Tolerability and immunogenicity in humans. Hum. Vaccin., 5, 475-482.
101. 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.; Ofori-Anyinam, O.; Ramboer, I.; Cahill, C.P.; Lievens, M.; Dubois, M.C.; Demoitie, M.A.; Leach, A.; Cohen, J.; Ballou, W.R. and Heppner, D.G. Jr. (2009) Evaluation of RTS, S/AS02A and RTS, S/AS01B in adults in a high malaria transmission area. PLoS One., 4, e6465.
102. Brichard, V.G. and Lejeune, D. (2008) Cancer immunotherapy targeting tumour-specific antigens: towards a new therapy for minimal residual disease. Expert. Opin. Biol. Ther., 8, 951-968.
103. Jiang, Z.H.; Budzynski, W.A.; Qiu, D.; Yalamati, D. and Koganty, R.R. (2007) Monophosphoryl lipid A analogues with varying 3-Osubstitution: synthesis and potent adjuvant activity. Carbohydr. Res., 342, 784-796.
104. Hawkins, L.D.; Ishizaka, S.T.; McGuinness, P.; Zhang, H.; Gavin, W.; DeCosta, B.; Meng, Z.; Yang, H.; Mullarkey, M.; Young, D.W.; Yang, H.; Rossignol, D.P.; Nault, A.; Rose, J.; Przetak, M.; Chow, J.C. and Gusovsky, F. (2002) A novel class of endotoxin receptor agonists with simplified structure, toll-like receptor 4-dependent immunostimulatory action, and adjuvant activity. J. Pharmacol. Exp. Ther., 300, 655-661.
105. Jiang, Z.H.; Bach, M.V.; Budzynski, W.A.; Krantz, M.J.; Koganty, R.R. and Longenecker, B.M. (2002) Lipid A structures containing novel lipid moieties: synthesis and adjuvant properties. Bioorg. Med. Chem. Lett., 12, 2193-2196.
106. Coler, R.N.; Bertholet, S.; Moutaftsi, M.; Guderian, J.A.; Windish, H.P.; Baldwin, S.L.; Laughlin, E.M.; Duthie, M.S.; Fox, C.B.; Carter, D.; Friede, M.; Vedvick, T.S. and Reed, S.G. (2011) Development and characterization of synthetic glucopyranosyl lipid adjuvant system as a vaccine adjuvant. PLoS One., 6, e16333.
107. Dupont, J.; Altclas, J.; Lepetic, A.; Lombardo, M.; Vazquez, V.; Salgueira, C.; Seigelchifer, M.; Arndtz, N.; Antunez, E.; von Eschen, K. and Janowicz, Z. (2006) A controlled clinical trial comparing the safety and immunogenicity of a new adjuvanted hepatitis B vaccine with a standard hepatitis B vaccine. Vaccine, 24, 7167-7174.
108. Zhu, D.; Barniak, V.; Zhang, Y.; Green, B. and Zlotnick, G. (2006) Intranasal immunization of mice with recombinant lipidated P2086 protein reduces nasal colonization of group B Neisseria meningitidis. Vaccine, 24, 5420-5425.
109. Ishizaka, S.T. and Hawkins, L.D. (2007) E6020: a synthetic Tolllike receptor 4 agonist as a vaccine adjuvant. Expert. Rev. Vaccines, 6, 773-784.
110. Morefield, G.L.; Hawkins, L.D.; Ishizaka, S.T.; Kissner, T.L. and Ulrich, R.G. (2007) Synthetic Toll-like receptor 4 agonist enhances vaccine efficacy in an experimental model of toxic shock syndrome. Clin. Vaccine Immunol., 14, 1499-1504.
111. Lousada-Dietrich, S.; Jogdand, P.S.; Jepsen, S.; Pinto, V.V.; Ditlev, S.B.; Christiansen, M.; Larsen, S.O.; Fox, C.B.; Raman, V.S.; Howard, R.F.; Vedvick, T.S.; Ireton, G.; Carter, D.; Reed, S.G. and Theisen, M. (2011) A synthetic TLR4 agonist formulated in an emulsion enhances humoral and Type 1 cellular immune responses against GMZ2--a GLURP-MSP3 fusion protein malaria vaccine candidate. Vaccine, 29, 3284-3292.
112. Cong, H.; Mui, E.J.; Witola, W.H.; Sidney, J.; Alexander, J.; Sette, A.; Maewal, A. and McLeod, R. (2011) Towards an immunosense vaccine to prevent toxoplasmosis: protective Toxoplasma gondii epitopes restricted by HLA-A*0201. Vaccine, 29, 754-762.
113. Coler, R.N.; Baldwin, S.L.; Shaverdian, N.; Bertholet, S.; Reed, S.J.; Raman, V.S.; Lu, X.; DeVos, J.; Hancock, K.; Katz, J.M.; Vedvick, T.S.; Duthie, M.S.; Clegg, C.H.; Van Hoeven, N. and Reed, S.G. (2010) A synthetic adjuvant to enhance and expand immune responses to influenza vaccines. PLoS One., 5, e13677.
114. Bertholet, S.; Ireton, G.C.; Ordway, D.J.; Windish, H.P.; Pine, S.O.; Kahn, M.; Phan, T.; Orme, I.M.; Vedvick, T.S.; Baldwin, S.L.; Coler, R.N. and Reed, S.G. (2010) A defined tuberculosis vaccine candidate boosts BCG and protects against multidrugresistant Mycobacterium tuberculosis. Sci. Transl. Med., 2, 53ra74.
115. Ueda, H. and Yamazaki, M. (1997) Induction of tumor necrosis factor in a murine tumor by systemic administration of a novel synthetic lipid A analogue, ONO-4007. J. Immunother., 20, 65-69.
116. Matsumoto, N.; Aze, Y.; Akimoto, A. and Fujita, T. (1997) Restoration of immune responses in tumor-bearing mice by ONO-4007, an antitumor lipid A derivative. Immunopharmacol., 36, 69-78.
117. Khan, M.A.; Maruno, M.; Khaskhely, N.M.; Ramzi, S.T.; Hosokawa, A.; Uezato, H.; Landires, E.A.; Hashiguchi, Y. and Nonaka, S. (2002) Inhibition of intracellular proliferation of Leishmania parasites in vitro and suppression of skin lesion development in BALB/c mice by a novel lipid A analog (ONO-4007). Am. J. Trop. Med. Hyg., 67, 184-190.
118. Calvopina, M.; Barroso, P.A.; Marco, J.D.; Korenaga, M.; Cooper, P.J.; Nonaka, S. and Hashiguchi, Y. (2006) Efficacy of vaccination with a combination of Leishmania amastigote antigens and the lipid A-analogue ONO-4007 for immunoprophylaxis and immunotherapy against Leishmania amazonensis infection in a murine model of New World cutaneous leishmaniasis. Vaccine, 24, 5645-5652.
119. van de Waterbeemd, B.; Streefland, M.; van der Ley, P.; Zomer, B.; van Dijken, H.; Martens, D.; Wijffels, R. and van der Pol, L. (2010) Improved OMV vaccine against Neisseria meningitidis using genetically engineered strains and a detergent-free purification process. Vaccine, 28, 4810-4816.
120. van der Ley, P.; Steeghs, L.; Hamstra, H.J.; Ten Hove, J.; Zomer, B. and van Alphen, L. (2001) Modification of lipid A biosynthesis in Neisseria meningitidis lpxL mutants: influence on lipopolysaccharide structure, toxicity, and adjuvant activity. Infect. Immun., 69, 5981-5990.
121. Arenas, J.; van Dijken, H.; Kuipers, B.; Hamstra, H.J.; Tommassen, J. and van der Ley, P. (2010) Coincorporation of LpxL1 and PagL mutant lipopolysaccharides into liposomes with Neisseria meningitidis opacity protein: influence on endotoxic and adjuvant activity. Clin. Vaccine Immunol., 17, 487-495.
122. Arigita, C.; Luijkx, T.; Jiskoot, W.; Poelen, M.; Hennink, W.E.; Crommelin, D.J.; van der Ley, P.; Els, C. and Kersten, G.F. (2005) Well-defined and potent liposomal meningococcal B vaccines adjuvated with LPS derivatives. Vaccine, 23, 5091-5098.
123. Jain, V.; Sahu, R.; Misra-Bhattacharya, S.; Vyas, S.P. and Kohli, D. (2008) Enhancement of T-helper type I immune responses against hepatitis B surface antigen by LPS derivatives adjuvanted liposomes delivery system. J. Drug Target, 16, 706-715.
124. Steeghs, L.; Keestra, A.M.; van Mourik, A.; Uronen-Hansson, H.; van der Ley, P.; Callard, R.; Klein, N. and van Putten, J.P. (2008) Differential activation of human and mouse Toll-like receptor 4 by the adjuvant candidate LpxL1 of Neisseria meningitidis. Infect. Immun., 76, 3801-3807.
125. Keiser, P.B.; Biggs-Cicatelli, S.; Moran, E.E.; Schmiel, D.H.; Pinto, V.B.; Burden, R.E.; Miller, L.B.; Moon, J.E.; Bowden, R.A.; Cummings, J.F. and Zollinger, W.D. (2011) A phase 1 study of a meningococcal native outer membrane vesicle vaccine made from a group B strain with deleted lpxL1 and synX, over-expressed factor H binding protein, two PorAs and stabilized OpcA expression. Vaccine, 29, 1413-1420.
126. Geurtsen, J.; Banus, H.A.; Gremmer, E.R.; Ferguson, H.; de la Fonteyne-Blankestijn, L.J.; Vermeulen, J.P.; Dormans, J.A.; Tommassen, J.; van der Ley, P.; Mooi, F.R. and Vandebriel, R.J. (2007) Lipopolysaccharide analogs improve efficacy of acellular pertussis vaccine and reduce type I hypersensitivity in mice. Clin. Vaccine Immunol., 14, 821-829.
127. Kawasaki, K.; Ernst, R.K. and Miller, S.I. (2005) Purification and characterization of deacylated and/or palmitoylated lipid A species unique to Salmonella enterica serovar Typhimurium. J. Endotoxin. Res., 11, 57-61.
128. Asensio, C.J.; Gaillard, M.E.; Moreno, G.; Bottero, D.; Zurita, E.; Rumbo, M.; van der Ley, P.; van der Ark, A. and Hozbor, D. (2011) Outer membrane vesicles obtained from Bordetella pertussis Tohama expressing the lipid A deacylase PagL as a novel acellular vaccine candidate. Vaccine, 29, 1649-1656.
129. Kato, N.; Kido, N.; Ohta, M. and Naito, S. (1985) Comparative studies on adjuvanticity of Klebsiella O3 lipopolysaccharide and its lipid A and polysaccharide fractions. Immunology, 54, 317-324.
130. Kido, N.; Ohta, M.; Ito, H.; Naito, S.; Nagase, F.; Nakashima, I. and Kato N. (1985) Potent adjuvant action of lipopolysaccharides possessing the O-specific polysaccharide moieties consisting of mannans in antibody response against protein antigen. Cell Immunol., 91, 52-59.
131. Chen, W.; Patel, G.B.; Yan, H. and Zhang, J. (2010) Recent advances in the development of novel mucosal adjuvants and antigen delivery systems. Hum. Vaccin., 17, 9.
132. De Temmerman, M.L.; Rejman, J.; Demeester, J.; Irvine, D.J.; Gander, B. and De Smedt, S.C. (2011) Particulate vaccines: on the quest for optimal delivery and immune response. Drug Discov. Today, 16, 569-582.
133. Sanchez, S.; Troncoso, G.; Ferreiros, C.M. and Criado, M.T. (2001) Evaluation of cross-reactive antigens as determinants of cross-bactericidal activity in pathogenic and commensal Neisseria. Vaccine, 19, 3390-3398.
134. Henriksen-Lacey, M.; Korsholm, K.S.; Andersen, P.; Perrie, Y. and Christensen, D. (2011) Liposomal vaccine delivery systems. Expert. Opin. Drug Deliv., 8, 505-519.
135. Roy, P. and Noad, R. (2009) Virus-like particles as a vaccine delivery system: myths and facts. Adv. Exp. Med. Biol., 655, 145-158.
136. Faisal, S.M.; Chen, J.W.; McDonough, S.P.; Chang, C.F.; Teng, C.H. and Chang, Y.F. (2011) Immunostimulatory and antigen delivery properties of liposomes made up of total polar lipids from non-pathogenic bacteria leads to efficient induction of both innate and adaptive immune responses. Vaccine, 29, 2381-2391.
137. Christensen, D.; Korsholm, K.S.; Andersen, P. and Agger, E.M. (2011) Cationic liposomes as vaccine adjuvants. Expert. Rev. Vaccines, 10, 513-521.
138. Arigita, C.; Kersten, G.F.; Hazendonk, T.; Hennink, W.E.; Crommelin, D.J. and Jiskoot, W. (2003) Restored functional immunogenicity of purified meningococcal PorA by incorporation into liposomes. Vaccine, 21, 950-960.
139. Christodoulides, M.; Brooks, J.L.; Rattue, E. and Heckels, J.E. (1998) Immunization with recombinant class 1 outer-membrane protein from Neisseria meningitidis: influence of liposomes and adjuvants on antibody avidity, recognition of native protein and the induction of a bactericidal immune response against meningococci. Microbiology, 144 (Pt 11), 3027-3037.
140. de Jonge, M.I.; Vidarsson, G.; van Dijken, H.H.; Hoogerhout, P.; van Alphen, L.; Dankert, J. and van der Ley, P. (2003) Functional activity of antibodies against the recombinant OpaJ protein from Neisseria meningitidis. Infect. Immun., 71, 2331-2340.
141. Dijkstra, J.; Mellors, J.W.; Ryan, J.L. and Szoka, F.C. (1987) Modulation of the biological activity of bacterial endotoxin by incorporation into liposomes. J. Immunol., 138, 2663-2670.
142. Dijkstra, J.; Larrick, J.W.; Ryan, J.L. and Szoka, F.C. (1988) Incorporation of LPS in liposomes diminishes its ability to induce tumoricidal activity and tumor necrosis factor secretion in murine macrophages. J. Leukoc. Biol., 43, 436-444.
143. Petrov, A.B.; Semenov, B.F.; Vartanyan, Y.P.; Zakirov, M.M.; Torchilin, V.P.; Koshkina, N.V.; L'Vov, V.L.; Verner, I.K.; Lopyrev, I.V., et al. (1992) Toxicity and immunogenicity of Neisseria meningitidis lipopolysaccharide incorporated into liposomes. Infect. Immun., 60, 3897-3903.
144. Fisseha, M.; Chen, P.; Brandt, B.; Kijek, T.; Moran, E. and Zollinger, W. (2005) Characterization of native outer membrane vesicles from lpxL mutant strains of Neisseria meningitidis for use in parenteral vaccination. Infect. Immun., 73, 4070-4080.
145. Mirlashari, M.R. and Lyberg, T. (2003) Expression and involvement of Toll-like receptors (TLR)2, TLR4, and CD14 in monocyte TNF-alpha production induced by lipopolysaccharides from Neisseria meningitidis. Med. Sci. Monit., 9, BR316-BR324.
146. de Vries, J.J.; Bungener, L.; Ter Veer W.; van Alphen, L.; van der Ley, P.; Wilschut, J. and Huckriede, A. (2009) Incorporation of LpxL1, a detoxified lipopolysaccharide adjuvant, in influenza H5N1 virosomes increases vaccine immunogenicity. Vaccine, 27, 947-955.
147. Heppner, D.G.; Gordon, D.M.; Gross, M.; Wellde, B.; Leitner, W.; Krzych, U.; Schneider, I.; Wirtz, R.A.; Richards, R.L.; Trofa, A.; Hall, T.; Sadoff, J.C.; Boerger, P.; Alving, C.R.; Sylvester, D.R.; Porter, T.G. and Ballou, W.R. (1996) Safety, immunogenicity, and efficacy of Plasmodium falciparum repeatless circumsporozoite protein vaccine encapsulated in liposomes. J. Infect. Dis., 174, 361-366.
148. Vandepapeliere, P.; Horsmans, Y.; Moris, P.; Van Mechelen, M.; Janssens, M.; Koutsoukos, M. Van Belle, P.; Clement, F.; Hanon, E.; Wettendorff, M.; Garçon, N. and Leroux-Roels, G. (2008) Vaccine adjuvant systems containing monophosphoryl lipid A and QS21 induce strong and persistent humoral and T cell responses against hepatitis B surface antigen in healthy adult volunteers. Vaccine, 26, 1375-1386.
149. Olson, K.; Macias, P.; Hutton, S.; Ernst, W.A.; Fujii, G. and Dler-Moore, J.P. (2009) Liposomal gD ectodomain (gD1-306) vaccine protects against HSV2 genital or rectal infection of female and male mice. Vaccine, 28, 548-560.
150. Hall, M.A.; Stroop, S.D.; Hu, M.C.; Walls, M.A.; Reddish, M.A.; Burt, D.S.; Lowell, G.H. and Dale, J.B. (2004) Intranasal immunization with multivalent group A streptococcal vaccines protects mice against intranasal challenge infections. Infect. Immun., 72, 2507-2512.
151. Tana; Watarai, S.; Isogai, E. and Oguma, K. (2003) Induction of intestinal IgA and IgG antibodies preventing adhesion of verotoxinproducing Escherichia coli to Caco-2 cells by oral immunization with liposomes. Lett. Appl. Microbiol., 36, 135-139.
152. Taylor, B.; Wadsworth, J.; Wadsworth, M. and Peckham, C. (1984) Changes in the reported prevalence of childhood eczema since the 1939-45 war. lancet, 2, 1255-1257.
153. Fleming, D.M. and Crombie, D.L. (1987) Prevalence of asthma and hay fever in England and Wales. Br. Med. J. (Clin. Res. Ed)., 294, 279-283.
154. Strachan, D.P. (1989) Hay fever, hygiene, and household size. BMJ, 299, 1259-1260.
155. Von Ehrenstein, O.S.; Von Mutius, E.; Illi, S.; Baumann, L.; Bohm, O. and Von Kries, R. (2000) Reduced risk of hay fever and asthma among children of farmers. Clin. Exp. Allergy, 30, 187-193.
156. Riedler, J.; Braun-Fahrlander, C.; Eder, W.; Schreuer, M.; Waser, M.; Maisch, S.; Carr, D.; Schierl, R.; Nowak, D.; Von Mutius, E. and ALEX Study Team. (2001) Exposure to farming in early life and development of asthma and allergy: a cross-sectional survey. lancet, 358, 1129-1133.
157. Aumeunier, A.; Grela, F.; Ramadan, A.; Pham, V.L.; Bardel, E.; Gomez, A.A.; Jeannin, P.; Akira, S.; Bach, J.F. and Thieblemont, N. (2010) Systemic Toll-like receptor stimulation suppresses experimental allergic asthma and autoimmune diabetes in NOD mice. PLoS One., 5, e11484.
158. Tian, J.; Zekzer, D.; Hanssen, L.; Lu, Y.; Olcott, A. and Kaufman, D.L. (2001) Lipopolysaccharide-activated B cells down-regulate Th1 immunity and prevent autoimmune diabetes in nonobese diabetic mice. J. Immunol., 167, 1081-1089.
159. Magnan, A.O.; Mely, L.G.; Camilla, C.A.; Badier, M.M.; Montero-Julian, F.A.; Guillot, C.M.; Casano, B.B.; Prato, S.J.; Fert, V.; Bongrand, P. and Vervloet, D. (2000) Assessment of the Th1/Th2 paradigm in whole blood in atopy and asthma. Increased IFNgamma-producing CD8(+) T cells in asthma. Am. J. Respir. Crit. Care Med., 161, 1790-1796.
160. Rietschel, E.T.; Kirikae, T.; Schade, F.U.; Mamat, U.; Schmidt, G.; Loppnow, H.; Ulmer, A.J.; Zähringer, U.; Seydel, U.; Di Padova, F.; et al. (1994) Bacterial endotoxin: molecular relationships of structure to activity and function. FASEB J., 8, 217-225.
161. Cox, L. and Wallace, D. (2011) Specific allergy immunotherapy for allergic rhinitis: subcutaneous and sublingual. Immunol Allergy Clin. North Am., 31, 561-599.
162. Calderon, M.A.; Penagos, M.; Sheikh, A.; Canonica, G.W. and Durham, S. (2011) Sublingual immunotherapy for treating allergic conjunctivitis. Cochrane. Database. Syst. Rev., 7, CD007685.
163. Akkoc, T.; Akdis, M. and Akdis, C.A. (2011) Update in the mechanisms of allergen-specific immunotheraphy. Allergy Asthma Immunol Res., 3, 11-20.
164. Hollingsworth, J.W.; Whitehead, G.S.; Lin, K.L.; Nakano, H.; Gunn, M.D.; Schwartz, D.A. and Cook, D.N. (2006) TLR4 signaling attenuates ongoing allergic inflammation. J. Immunol., 176, 5856-5862.
165. Drachenberg, K.J.; Wheeler, A.W.; Stuebner, P. and Horak, F. (2001) A well-tolerated grass pollen-specific allergy vaccine containing a novel adjuvant, monophosphoryl lipid A, reduces allergic symptoms after only four preseasonal injections. Allergy, 56, 498-505.
166. Drachenberg, K.J.; Heinzkill, M.; Urban, E. and Woroniecki, S.R. (2003) Efficacy and tolerability of short-term specific immunotherapy with pollen allergoids adjuvanted by monophosphoryl lipid A (MPL) for children and adolescents. Allergol. Immunopathol (Madr), 31, 270-277.
167. Tsukioka, D.; Nishizawa, T.; Miyase, T.; Achiwa, K.; Suda, T.; Soma, G. and Mizuno, D. (1997) Structural characterization of lipid A obtained from Pantoea agglomerans lipopolysaccharide. FEMS Microbiol Lett., 149, 239-244.
168. Yoshida, A.; Kohchi, C.; Inagawa, H.; Nishizawa, T. and Soma, G. (2009) Improvement of allergic dermatitis via regulation of the Th1/Th2 immune system balance by macrophages activated with lipopolysaccharide derived from Pantoea agglomerans (IP-PA1). Anticancer Res., 29, 4867-4870.
169. Hebishima, T.; Matsumoto, Y.; Watanabe, G.; Soma, G.; Kohchi, C.; Taya, K.; Hayashi, Y. and Hirota, Y. (2010) Protective effects of the immunopotentiator from Pantoea agglomerans 1 on chemotherapeutic agent-induced macrophage growth inhibition. Anticancer Res., 30, 2033-2040.
170. Goto, S.; Sakai, S.; Kera, J.; Suma, Y.; Soma, G.I. and Takeuchi, S. (1996) Intradermal administration of lipopolysaccharide in treatment of human cancer. Cancer Immunol. Immunother., 42, 255-261.
171. Hebishima, T.; Matsumoto, Y.; Watanabe, G.; Soma, G.; Kohchi, C.; Taya, K.; Hayashi, Y. and Hirota, Y. (2010) Recovery from immunosuppression-related disorders in humans and animals by IP-PA1, an edible lipopolysaccharide. Anticancer Res., 30, 3113-3118.
172. Hebishima, T.; Matsumoto, Y.; Soma, G.; Kohchi, C.; Watanabe, G.; Taya, K.; Hayashi, Y. and Hirota, Y. (2010) Immune recovery effects of immunopotentiator from Pantoea agglomerans 1 (IPPA1) on low antibody productions in response to Salmonella enteritidis vaccine and sheep red blood cells in dexamethasonetreated stressed chicken models. J. Vet. Med. Sci., 72, 435-442.
173. Kohchi, C.; Inagawa, H.; Nishizawa, T.; Yamaguchi, T.; Nagai, S. and Soma, G. (2006) Applications of lipopolysaccharide derived from Pantoea agglomerans (IP-PA1) for health care based on macrophage network theory. J. Biosci. Bioeng., 102, 485-496.
174. Okutomi, T. and Suzuki, T. (1995) [Immunomodulator as medicine for morphine and cocaine dependence. Especially effect of LPS]. Yakugaku Zasshi, 115, 42-51.
175. Okutomi, T.; Nishizawa, T.; Inagawa, H.; Soma, G.; Minami, M.; Satoh, M. and Mizuno D. (1992) Inhibition of morphine dependence by a lipopolysaccharide from Pantoea agglomerans. Eur. Cytokine Netw., 3, 417-420.
176. Freeman, B.D. and Natanson, C. (2000) Anti-inflammatory therapies in sepsis and septic shock. Expert. Opin. Investig. Drugs, 9, 1651-1663.
177. Greenberg, R.N.; Wilson, K.M.; Kunz, A.Y.; Wedel, N.I. and Gorelick, K.J. (1992) Observations using antiendotoxin antibody (E5) as adjuvant therapy in humans with suspected, serious, gramnegative sepsis. Crit. Care Med., 20, 730-735.
178. Harkonen, S.; Scannon, P.; Mischak, R.P.; Spitler, L.E.; Foxall, C.; Kennedy, D. and Greenberg, R. (1988) Phase I study of a murine monoclonal anti-lipid A antibody in bacteremic and nonbacteremic patients. Antimicrob. Agents Chemother., 32, 710-716.
179. Wittebole, X.; Castanares-Zapatero, D. and Laterre, P.F. (2010) Toll-like receptor 4 modulation as a strategy to treat sepsis. Mediators. Inflamm., 2010, 568396.
180. Lynn, W.A. and Golenbock, D.T. (1992) Lipopolysaccharide antagonists. Immunol. Today, 13, 271-276.
181. Christ, W.J.; Asano, O.; Robidoux, A.L.; Perez, M.; Wang, Y.; Dubuc, G.R.; et al. (1995) E5531, a pure endotoxin antagonist of high potency. Science, 268, 80-83.
182. Kim, H.M.; Park, B.S.; Kim, J.I.; Kim, S.E.; Lee, J.; Oh, S.C.; Enkhbayar, P.; Matsushima, N.; Lee, H.; Yoo, O.J. and Lee, J.O. (2007) Crystal structure of the TLR4-MD-2 complex with bound endotoxin antagonist Eritoran. Cell, 130, 906-917.
183. Bunnell, E.; Lynn, M.; Habet, K.; Neumann, A.; Perdomo, C.A.; Friedhoff, L.T.; Rogers, S.L. and Parrillo, J.E. (2000) A lipid A analog, E5531, blocks the endotoxin response in human volunteers with experimental endotoxemia. Crit. Care Med., 28, 2713-2720.
184. Rose, J.R.; Mullarkey, M.A.; Christ, W.J.; Hawkins, L.D.; Lynn, M.; Kishi, Y.; Wasan, K.M.; Peteherych, K. and Rossignol, D.P. (2000) Consequences of interaction of a lipophilic endotoxin antagonist with plasma lipoproteins. Antimicrob. Agents Chemother., 44, 504-510.
185. Barochia, A.; Solomon, S.; Cui, X.; Natanson, C. and Eichacker, P.Q. (2011) Eritoran tetrasodium (E5564) treatment for sepsis: review of preclinical and clinical studies. Expert. Opin. Drug Metab. Toxicol., 7, 479-494.
186. Mullarkey, M.; Rose, J.R.; Bristol, J.; Kawata, T.; Kimura, A.; Kobayashi, S.; Przetak, M.; Chow, J.; Gusovsky, F.; Christ, W.J. and Rossignol, D.P. (2003) Inhibition of endotoxin response by e5564, a novel Toll-like receptor 4-directed endotoxin antagonist. J. Pharmacol. Exp. Ther., 304, 1093-1102.
187. Rossignol, D.P.; Wong, N.; Noveck, R. and Lynn, M. (2008) Continuous pharmacodynamic activity of eritoran tetrasodium, a TLR4 antagonist, during intermittent intravenous infusion into normal volunteers. Innate. Immun., 14, 383-394.
188. Savov, J.D.; Brass, D.M.; Lawson, B.L.; Elvania-Tekippe, E.; Walker, J.K. and Schwartz, D.A. (2005) Toll-like receptor 4 antagonist (E5564) prevents the chronic airway response to inhaled lipopolysaccharide. Am. J. Physiol. Lung Cell Mol. Physiol., 289, L329-L337.
189. Sun, Y. and Pearlman, E. (2009) Inhibition of corneal inflammation by the TLR4 antagonist Eritoran tetrasodium (E5564). Invest. Ophthalmol. Vis. Sci., 50, 1247-1254.
190. Guha, M. and Mackman, N. (2001) LPS induction of gene expression in human monocytes. Cell Signal., 13, 85-94.
191. Edfeldt, K.; Swedenborg, J.; Hansson, G.K. and Yan, Z.Q. (2002) Expression of toll-like receptors in human atherosclerotic lesions: a possible pathway for plaque activation. Circulation, 105, 1158-1161.
192. De Jager, P.L.; Franchimont, D.; Waliszewska, A.; Bitton, A.; Cohen, A.; Langelier, D.; Belaiche, J.; Vermeire, S.; Farwell, L.; Goris, A.; Libioulle, C.; Jani, N.; Dassopoulos, T.; Bromfield, G.P.; Dubois, B.; Cho, J.H.; Brant, S.R.; Duerr, R.H.; Yang, H.; Rotter, J.I.; Silverberg, M.S.; Steinhart, A.H.; Daly, M.J.; Podolsky, D.K.; Louis, E.; Hafler, D.A.; Rioux, J.D. and Quebec IBD Genetics Consortium; NIDDK IBD Genetics Consortium. (2007) The role of the Toll receptor pathway in susceptibility to inflammatory bowel diseases. Genes Immun., 8, 387-397.
193. Bazin, H.G.; Murray, T.J.; Bowen, W.S.; Mozaffarian, A.; Fling, S.P.; Bess, L.S.; Livesay, M.T.; Arnold, J.S.; Johnson, C.L.; Ryter, K.T.; Cluff, C.W.; Evans, J.T. and Johnson, D.A. (2008) The 'Ethereal' nature of TLR4 agonism and antagonism in the AGP class of lipid A mimetics. Bioorg. Med. Chem. Lett., 18, 5350-5354.
194. Fort, M.M.; Mozaffarian, A.; Stover, A.G.; Correia, J.S.; Johnson, D.A.; Crane, R.T.; Ulevitch, R.J.; Persing, D.H.; Bielefeldt-Ohmann, H.; Probst, P.; Jeffery, E.; Fling, S.P. and Hershberg, R.M. (2005) A synthetic TLR4 antagonist has anti-inflammatory effects in two murine models of inflammatory bowel disease. J. Immunol., 174, 6416-6423.
195. Leon, C.G.; Tory, R.; Jia, J.; Sivak, O. and Wasan, K.M. (2008) Discovery and development of toll-like receptor 4 (TLR4) antagonists: a new paradigm for treating sepsis and other diseases. Pharm. Res., 25, 1751-1761.