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Immunological Foundations to the Quest for New Vaccine Adjuvants

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Abstract

Developing efficient adjuvants for human vaccines that elicit broad and sustained immune responses at systemic or mucosal levels remains a formidable challenge for the vaccine industry. Conventional approaches in the past have been largely empirical and — at best — partially successful. Importantly, recent advances in our understanding of the immune system, most particularly with respect to early proinflammatory signals, are leading to the identification of new biological targets for vaccine adjuvants. This review covers both the current status of adjuvant testing in humans, the residual needs for vaccines in development, and the emerging immunological foundations for adjuvant design. A better understanding of the biology of toll-like receptors, non-conventional T cell subpopulations, T and B cell memory, regulatory T cells, and mucosal immunity has profound implications for a modern approach to adjuvant screening and development. The future lies in the high throughput screening of synthetic chemical entities targeting well-characterized biological molecules. Used alone or in combination, such synthetic adjuvants will allow stimulation or modulation in a safe and efficient manner of strong effector, regulatory and memory immune mechanisms.

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References

  1. Schijns V. Immunological concepts of vaccine adjuvant activity. Curr Opin Immunol 2000; 12: 456–63

    Article  PubMed  CAS  Google Scholar 

  2. Vogel FR. Improving vaccine performance with adjuvants. Clin Infect Dis 2000; 30Suppl. 3: S266–70

    Article  PubMed  CAS  Google Scholar 

  3. Moingeon P, Haensler J, Lindberg A. Towards the rational design of Thl adjuvants. Vaccine 2001; 19: 4363–72

    Article  PubMed  CAS  Google Scholar 

  4. Moingeon P. Strategies for designing vaccines eliciting Th1 responses in humans. J Biotechnol 2002; 98: 189–98

    Article  PubMed  CAS  Google Scholar 

  5. Czerkinsky C, Anjuere F, McGhee J, et al. Mucosal immunity and tolerance: relevance to vaccine development. Immunol Rev 1999; 170: 197–222

    Article  PubMed  CAS  Google Scholar 

  6. Hunter RL. Overview of vaccine adjuvants: present and future. Vaccine 2002; 20Suppl. 3: S7–12

    CAS  Google Scholar 

  7. Engers H, Kieny MP, Malhotra P, et al. Third meeting on novel adjuvants currently in or close to clinical testing. Vaccine 2003; 81: 3503–24

    Google Scholar 

  8. Persing DH, Coler RN, Lacy MJ, et al. Taking toll: lipid A mimetics as adjuvants and immunomodulators. Trends Microbiol 2002; 10(10 Suppl.): S32–7

    Article  PubMed  CAS  Google Scholar 

  9. Aguado T, Engers H, Pang T, et al. Novel adjuvants currently in clinical testing: November 2–4 1998, Fondation Mérieux, Annecy, France. A meeting sponsored by the World Health Organization. Vaccine 1999; 17: 2321–8

    Article  PubMed  CAS  Google Scholar 

  10. Saul A, Lawrence G, Smillie A, et al. Human phase I vaccine trials of 3 recombinant asexual stage malaria antigens with Montanide ISA720 adjuvant. Vaccine 1999; 17: 3145–59

    Article  PubMed  CAS  Google Scholar 

  11. Evans TG, Hasan M, Galibert L, et al. The use of Flt3 ligand as an adjuvant for hepatitis B vaccination of healthy adults. Vaccine 2002; 21: 322–9

    Article  PubMed  CAS  Google Scholar 

  12. Moingeon P, De Taisne C, Almond J. Delivery technologies for human vaccines. Br Med Bull 2002; 62: 29–44

    Article  PubMed  Google Scholar 

  13. Edelman R. The development and use of vaccine adjuvants. Mol Biotechnol 2002; 21(2): 129–48

    Article  PubMed  CAS  Google Scholar 

  14. Aujame L, Burdin N, Vicani M. How microarrays can improve our understanding of immune responses and vaccine development. Ann N Y Acad sci 2002; 975: 1–23

    Article  PubMed  CAS  Google Scholar 

  15. Berzofsky JA, Ahlers JD, Belyakov IM. Strategies for designing and optimizing new generation vaccines. Nat Rev Immunol 2001; 1(3): 209–19

    Article  PubMed  CAS  Google Scholar 

  16. Takeda K, Kaisho T, Akira S. Toll-like receptors. Annu Rev Immunol 2003; 21: 335–76

    Article  PubMed  CAS  Google Scholar 

  17. Janeway Jr CA, Medzhitov R. Innate immune recognition. Annu Rev Immunol 2002; 20: 197–216

    Article  PubMed  CAS  Google Scholar 

  18. Zlotnik A, Yoshie O. Chemokines: a new classification system and their role in immunity. Immunity 2000; 12: 121–7

    Article  PubMed  CAS  Google Scholar 

  19. Sallusto F, Schaerli P, Loetscher P, et al. Rapid and coordinated switch in chemokine receptor expression during dendritic cell maturation. Eur J Immunol 1998; 28: 2760–9

    Article  PubMed  CAS  Google Scholar 

  20. Sozzani L, Sallusto F, Luini W, et al. Migration of dendritic cells in response to formyl peptides, C5a, and a distinct set of chemokines. J Immunol 1995; 155(7): 3292–5

    PubMed  CAS  Google Scholar 

  21. Biragyn A, Tani K, Grimm M, et al. Genetic fusion of chemokines to a self tumor antigen induces protective, T-cell dependent antitumor immunity. Nat Biotechnol 1999; 17: 253–8

    Article  PubMed  CAS  Google Scholar 

  22. Sallusto F, Lanzavecchia A, Mackay CR. Chemokines and chemokine receptors in T-cell priming and Th1/Th2-mediated responses. Immunol Today 1998; 19(12): 568–74

    Article  PubMed  CAS  Google Scholar 

  23. Martin MU, Wesche H. Summary and comparison of the signaling mechanisms of the Toll/interleukin-1 receptor family. Biochim Biophys Acta 2002; 1592(3): 265–80

    Article  PubMed  CAS  Google Scholar 

  24. Krieg AM. CpG motifs in bacterial DNA and their immune effects. Annu Rev Immunol 2002; 20: 709–30

    Article  PubMed  CAS  Google Scholar 

  25. Hemmi H, Kaisho T, Takeuchi O, et al. Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway. Nat Immunol 2002; 3(2): 196–200

    Article  PubMed  CAS  Google Scholar 

  26. Kadowaki N, Ho S, Antonenko S, et al. Subsets of human dendritic cell precursors express different Toll-like receptors and respond to different microbial antigens. J Exp Med 2001; 194: 863–9

    Article  PubMed  CAS  Google Scholar 

  27. Ronaghy A, Prakken BJ, Takabayashi K, et al. Immunostimulatory DNA sequences influence the course of adjuvant arthritis. J Immunol 2002; 168(1): 51–6

    PubMed  CAS  Google Scholar 

  28. Schwartz DA, Quinn TJ, Thorne PS, et al. CpG motifs in bacterial DNA cause inflammation in the lower respiratory tract. J Clin Invest 1997; 100(1): 68–73

    Article  PubMed  CAS  Google Scholar 

  29. Bendelac A, Bonneville M, Kearney JF. Autoreactivity by design: innate B and T lymphocytes. Nat Rev Immunol 2001; 1(3): 177–86

    Article  PubMed  CAS  Google Scholar 

  30. Kronenberg M, Gapin L. The unconventional lifestyle of NKT cells. Nat Rev Immunol 2002; 2(8): 557–68

    PubMed  CAS  Google Scholar 

  31. Burdin N, Kronenberg M. CD 1-mediated immune responses to glycolipids. Curr Opin Immunol 1999; 11(3): 326–31

    Article  PubMed  CAS  Google Scholar 

  32. Gonzalez-Aseguinolaza G, Van Kaer L, Bergmann CC, et al. Natural killer T cell ligand alpha-galactosylceramide enhances protective immunity induced by malaria vaccines. J Exp Med 2002; 195(5): 617–24

    Article  PubMed  CAS  Google Scholar 

  33. Hayakawa Y, Takeda K, Yagita H, et al. Differential regulation of Th1 and Th2 functions of NKT cells by CD28 and CD40 costimulatory pathways. J Immunol 2001; 166(10): 6012–8

    PubMed  CAS  Google Scholar 

  34. Giaccone G, Punt CJ, Ando Y, et al. A phase I study of the natural killer T-cell ligand alpha-galactosylceramide (KRN7000) in patients with solid tumors. Clin Cancer Res 2002; 8(12): 3702–9

    PubMed  CAS  Google Scholar 

  35. Ferrarini M, Ferrero E, Dagna L, et al. Human gamma delta T cells: a nonredundant system in the immune-surveillance against cancer. Trends Immunol 2002; 23(1): 14–8

    Article  PubMed  CAS  Google Scholar 

  36. Carding SR, Egan PJ. Gamma delta T cells: functional plasticity and heterogeneity. Nat Rev Immunol 2002; 2(5): 336–45

    Article  PubMed  CAS  Google Scholar 

  37. Sireci G, Espinosa E, Di Sano C, et al. Differential activation of human gamma delta cells by nonpeptide phosphoantigens. Eur J Immunol 2001; 31(5): 1628–35

    Article  PubMed  CAS  Google Scholar 

  38. Espinosa E, Belmant C, Pont F, et al. Chemical synthesis and biological activity of bromohydrin pyrophosphate, a potent stimulator of human gamma delta T cells. J Biol Chem 2001; 276(21): 18337–44

    Article  PubMed  CAS  Google Scholar 

  39. Kaech SM, Wherry EJ, Ahmed R. Effector and memory T-cell differentiation: implications for vaccine development. Nat Rev Immunol 2002; 2(4): 251–62

    Article  PubMed  CAS  Google Scholar 

  40. Lanzavecchia A, Sallusto F. Progressive differentiation and selection of the fittest in the immune response. Nat Rev Immunol 2002; 2(12): 982–7

    Article  PubMed  CAS  Google Scholar 

  41. Lanzavecchia A, Sallusto F. Antigen decoding by T lymphocytes: from synapses to fate determination. Nat Immunol 2001; 2(6): 487–92

    Article  PubMed  CAS  Google Scholar 

  42. Hunter CA, Reiner SL. Cytokines and T cells in host defense. Curr Opin Immunol 2000; 12(4): 413–8

    Article  PubMed  CAS  Google Scholar 

  43. Sun JC, Bevan MJ. Defective CD8 T cell memory following acute infection without CD4 T cell help. Science 2003; 300(617): 339–42

    Article  PubMed  CAS  Google Scholar 

  44. Sprent J, Surh CD. Generation and maintenance of memory T cells. Curr Opin Immunol 2001; 13(2): 248–54

    Article  PubMed  CAS  Google Scholar 

  45. Badovinac VP, Tvinnereim AR, Harty JT. Regulation of antigen-specific CD8+ T cell homeostasis by perform and interferon-gamma. Science 2000; 290(5495): 1354–8

    Article  PubMed  CAS  Google Scholar 

  46. Badovinac VP, Porter BB, Harty JT. Programmed contraction of CD8 (+) T cells after infection. Nat Immunol 2002; 3(7): 619–26

    PubMed  CAS  Google Scholar 

  47. Westermann J, Ehlers EM, Exton MS, et al. Migration of naive, effector and memory T cells: implications for the regulation of immune responses. Immunol Rev 2001; 184: 20–37

    Article  PubMed  CAS  Google Scholar 

  48. Wherry EJ, Teichgraber V, Becker TC, et al. Lineage relationship and protective immunity of memory CD8 T cell subsets. Nat Immunol 2003; 4(3): 225–34

    Article  PubMed  CAS  Google Scholar 

  49. Kaech SM, Hemby S, Kersh E, et al. Molecular and functional profiling of memory CD8 T cell differentiation. Cell 2002; 111(6): 837–51

    Article  PubMed  CAS  Google Scholar 

  50. Opferman JT, Ober BT, Ashton-Rickardt PG. Linear differentiation of cytotoxic effectors into memory T lymphocytes. Science 1999; 283(5408): 1745–8

    Article  PubMed  CAS  Google Scholar 

  51. Ochsenbein AF, Karrer U, Klenerman P, et al. A comparison of T cell memory against the same antigen induced by virus versus intracellular bacteria. Proc Natl Acad sci U S A 1999; 96(16): 9293–8

    Article  PubMed  CAS  Google Scholar 

  52. Haglund K, Leiner I, Kerksiek K, et al. Robust recall and long-term memory T-cell responses induced by prime-boost regimens with heterologous live viral vectors expressing human immunodeficiency virus type 1 Gag and Env proteins. J Virol 2002; 76(15): 7506–17

    Article  PubMed  CAS  Google Scholar 

  53. Blattman JN, Grayson JM, Wherry EJ, et al. Therapeutic use of IL-2 to enhance antiviral T-cell responses in vivo. Nat Med 2003; 9: 540–7

    Article  PubMed  CAS  Google Scholar 

  54. Mitchell T, Hildeman D, Keoll R, et al. Immunological adjuvants promote activated T cell survival via induction of Bcl-3. Nat Immunol 2001; 2(5): 397–402

    PubMed  CAS  Google Scholar 

  55. Schluns KS, Lefrancois L. Cytokine control of memory T-cell development and survival. Nat Rev Immunol 2003; 3(4): 269–79

    Article  PubMed  CAS  Google Scholar 

  56. Manz RA, Arce S, Cassese G, et al. Humoral immunity and long-lived plasma cells. Curr Opin Immunol 2002; 14(4): 517–21

    Article  PubMed  CAS  Google Scholar 

  57. McHeyzer-Williams LJ, Driver DJ, McHeyzer-Williams MG. Germinal center reaction. Curr Opin Hematol 2001; 8(1): 52–9

    Article  PubMed  CAS  Google Scholar 

  58. Calame KL, Lin KI, Tunyaplin C. Regulatory mechanisms that determine the development and function of plasma cells. Annu Rev Immunol 2003; 21: 205–30

    Article  PubMed  CAS  Google Scholar 

  59. Walker LS, Gulbranson-Judge A, Flynn S, et al. Co-stimulation and selection for T-cell help for germinal centres: the role of CD28 and OX40. Immunol Today 2000; 21(7): 333–7

    Article  PubMed  CAS  Google Scholar 

  60. Bernasconi NL, Traggiai E, Lanzavecchia A. Maintenance of serological memory by polyclonal activation of human memory B cells. Science 2002; 298: 2199–202

    Article  PubMed  CAS  Google Scholar 

  61. Bluestone JA, Abbas AK. Natural versus adaptive regulatory T cells. Nat Rev Immunol 2003; 3(3): 253–7

    Article  PubMed  CAS  Google Scholar 

  62. Francois BJ. Regulatory T cells under scrutiny. Nat Rev Immunol 2003; 3(3): 189–98

    Article  Google Scholar 

  63. McGuirk P, Mills KH. Pathogen-specific regulatory T cells provoke a shift in the Th1/Th2 paradigm in immunity to infectious diseases. Trends Immunol 2002; 23(9): 450–5

    Article  PubMed  CAS  Google Scholar 

  64. Belkaid Y, Piccirillo CA, Mendez S, et al. CD4+CD25+ regulatory T cells control Leishmania major persistence and immunity. Nature 2002; 420(6915): 502–7

    Article  PubMed  CAS  Google Scholar 

  65. Piccirillo CA, Shevach EM. Cutting edge: control of CD8+ T cell activation by CD4+CD25+ immunoregulatory cells. J Immunol 2001; 167(3): 1137–40

    PubMed  CAS  Google Scholar 

  66. Lundgren A, Suri-Payer E, Enarsson K, et al. Helicobacter pylori-specific CD4 (+) CD25 (high) regulatory T cells suppress memory T-cell responses to H. pylori in infected individuals. Infect Immun 2003; 71(4): 1755–62

    Article  PubMed  CAS  Google Scholar 

  67. McGuirk P, McCann C, Mills KH. Pathogen-specific T regulatory 1 cells induced in the respiratory tract by a bacterial molecule that stimulates interleukin 10 production by dendritic cells: a novel strategy for evasion of protective T helper type 1 responses by Bordetella pertussis. J Exp Med 2002; 195(2): 221–31

    Article  PubMed  CAS  Google Scholar 

  68. Boussiotis VA, Tsai EY, Yunis EJ, et al. IL-10-producing T cells suppress immune responses in anergic tuberculosis patients. J Clin Invest 2000; 105(9): 1317–25

    Article  PubMed  CAS  Google Scholar 

  69. Jonuleit H, Schmitt E, Steinbrink K, et al. Dendritic cells as a tool to induce anergic and regulatory T cells. Trends Immunol 2001; 22(7): 394–400

    Article  PubMed  CAS  Google Scholar 

  70. Akbari O, Freeman GJ, Meyer EH, et al. Antigen-specific regulatory T cells develop via the ICOS-ICOS-ligand pathway and inhibit allergen-induced airway hyperreactivity. Nat Med 2002; 8(9): 1024–32

    Article  PubMed  CAS  Google Scholar 

  71. Sakaguchi S. Control of immune responses by naturally arising CD4+ regulatory T cells that express toll-like receptors. J Exp Med 2003; 197(4): 397–401

    Article  PubMed  CAS  Google Scholar 

  72. Caramalho I, Lopes-Carvalho T, Ostler D, et al. Regulatory T cells selectively express toll-like receptors and are activated by lipopolysaccharide. J Exp Med 2003; 197(4): 403–11

    Article  PubMed  CAS  Google Scholar 

  73. Pasare C, Medzhitov R. Toll pathway-dependent blockade of CD4+CD25+ T cell-mediated suppression by dendritic cells. Science 2003; 299(5609): 1033–6

    Article  PubMed  CAS  Google Scholar 

  74. Walker RI. New strategies for using mucosal vaccination to achieve more effective immunisation. Vaccine 1994; 12: 87–93

    Article  Google Scholar 

  75. Hathaway LJ, Kraehenbuhl JP. The role of M cells in mucosal immunity. Cell Mol Life sci 2000; 57(2): 323–32

    Article  PubMed  CAS  Google Scholar 

  76. Jump RL, Levine AD. Murine Peyer’s patches favor development of an IL-10-secreting, regulatory T cell population. J Immunol 2002; 168(12): 6113–9

    PubMed  CAS  Google Scholar 

  77. Alpan O, Rudomen G, Matzinger P. The role of dendritic cells, B cells, and M cells in gut-oriented immune responses. J Immunol 2001; 166(8): 4843–52

    PubMed  CAS  Google Scholar 

  78. Shreedhar VK, Kelsall BL, Neutra MR. Cholera toxin induces migration of dendritic cells from the subepithelial dome region to T- and B-cell areas of Peyer’s patches. Infect Immun 2003; 71(1): 504–9

    Article  PubMed  CAS  Google Scholar 

  79. Zhou F, Kraehenbuhl JP, Neutra M. Mucosal IgA response to rectally administered antigen formulated in IgA-coated liposomes. Vaccine 1995; 13: 637–44

    Article  PubMed  CAS  Google Scholar 

  80. Eldridge JH, Staas JK, Meulbroek JA, et al. Biodegradable microspheres as a vaccine delivery system. Mol Immunol 1991; 28: 287–94

    Article  PubMed  CAS  Google Scholar 

  81. Lambert JS, Keefer M, Mulligan MJ, et al. A Phase I safety and immunogenicity trial of UBI microparticulate monovalent HIV-1 MN oral peptide immunogen with parenteral boost in HIV-1 seronegative human subjects. Vaccine 2001; 19(23-24): 3033–42

    Article  PubMed  CAS  Google Scholar 

  82. Katz DE, DeLorimier AJ, Wolf MK, et al. Oral immunization of adult volunteers with microencapsulated enterotoxigenic Escherichia coli (ETEC) CS6 antigen. Vaccine 2003; 21(5-6): 341–6

    Article  PubMed  CAS  Google Scholar 

  83. Clark MA, Blair H, Liang L, et al. Targeting polymerised liposome vaccine carriers to intestinal M cells. Vaccine 2001; 20(1–2): 208–17

    Article  PubMed  CAS  Google Scholar 

  84. Wu Y, Wang X, Csencsits KL, et al. M cell-targeted DNA vaccination. Proc Natl Acad sci U S A 2001; 98(16): 9318–23

    Article  PubMed  CAS  Google Scholar 

  85. Lavelle EC, Grant G, Pusztai A, et al. Mucosal immunogenicity of plant lectins in mice. Immunology 2000; 99(1): 30–7

    Article  PubMed  CAS  Google Scholar 

  86. Nardelli-Haefliger D, Kraehenbuhl JP, Curtis III R, et al. Oral and rectal immunisation of adult female volunteers with a recombinant attenuated Salmonella typhi vaccine strain. Infect Immun 1996; 64: 5219–25

    PubMed  CAS  Google Scholar 

  87. Sizemore DR, Branstrom AA, Sadoff JC. Attenuated Shigella as a DNA delivery vehicle for DNA-mediated immunisation. Science 1995; 270: 299–302

    Article  PubMed  CAS  Google Scholar 

  88. DiPetrillo MD, Tibbetts T, Kleanthous H, et al. Safety and immunogenicity of phoP/phoQ-deleted Salmonella typhi expressing Helicobacter pylori urease in adult volunteers. Vaccine 1999; 18(5-6): 449–59

    Article  Google Scholar 

  89. De Geus B, Dol-Bosman M, Scholten JW, et al. A comparison of natural and recombinant cholera toxin B subunit as stimulatory factors in intranasal immunisation. Vaccine 1997; 15: 1110–8

    Article  PubMed  Google Scholar 

  90. Rappuoli R, Pizza M, Douce G, et al. Structure and mucosal adjuvanticity of cholera and Escherichia coli heat-labile enterotoxins. Immunol Today 1999; 20(11): 493–500

    Article  PubMed  CAS  Google Scholar 

  91. Baudner BC, Balland O, Giuliani MM, et al. Enhancement of protective efficacy following intranasal immunization with vaccine plus a nontoxic LTK63 mutant delivered with nanoparticles. Infect Immun 2002; 70(9): 4785–90

    Article  PubMed  CAS  Google Scholar 

  92. van Ginkel FW, Jackson RJ, Yuki Y, et al. The mucosal adjuvant cholera toxin redirects vaccine proteins into olfactory tissues. J Immunol 2000; 165(9): 4778–82

    PubMed  Google Scholar 

  93. Hagiwara Y, Iwasaki T, Asanuma H, et al. Effects of intranasal administration of cholera toxin (or Escherichia coli heat-labile enterotoxin) B subunits supplemented with a trace amount of the holotoxin on the brain. Vaccine 2001; 19(13-14): 1652–60

    Article  PubMed  CAS  Google Scholar 

  94. Hodge LM, Marinaro M, Jones HP, et al. Immunoglobulin A (IgA) responses and IgE-associated inflammation along the respiratory tract after mucosal but not systemic immunization. Infect Immun 2001; 69(4): 2328–38

    Article  PubMed  CAS  Google Scholar 

  95. Sun JB, Holmgren J, Czerkinsky C. Cholera toxin B subunit: an efficient transmucosal delivery system for induction of peripheral immunological tolerance. Proc Natl Acad sci U S A 1994; 91: 10795–800

    Article  PubMed  CAS  Google Scholar 

  96. McSorley S, Rask C, Pichot R, et al. Selective tolerization of Th1 like cells after nasal administration of a cholera toxoid-LACK antigen. Eur J Immunol 1998; 28: 424–30

    Article  PubMed  CAS  Google Scholar 

  97. Lillard Jr JW, Boyaka PN, Taub D, et al. RANTES potentiates antigen-specific mucosal immune responses. J Immunol 2001; 166(1): 162–9

    PubMed  CAS  Google Scholar 

  98. Staats HF, Ennis Jr FA. IL-1 is an effective adjuvant for mucosal and systemic immune responses when coadministered with protein immunogens. J Immunol 1999 May 15; 162(10): 6141–7

    PubMed  CAS  Google Scholar 

  99. McCluskie MJ, Weeratna RD, Payette PJ, et al. The potential of CpG oligodeox-ynucleotides as mucosal adjuvants. Crit Rev Immunol 2001; 21(1–3): 103–20

    PubMed  CAS  Google Scholar 

  100. Csencsits KL, Jutila MA, Pascual DW. Mucosal addressin expression and binding-interactions with naive lymphocytes vary among the cranial, oral, and nasal-associated lymphoid tissues. Eur J Immunol 2002; 32(11): 3029–39

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

The authors wish to thank Drs Jean Haensler and Emmanuelle Trannoy for their critical reading of the manuscript.

The authors are employed by the pharmaceutical industry but do not have any conflict of interest directly relevant to the content of this review.

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  1. Research and Development, Campus Mérieux, Aventis Pasteur, Marcy l’Etoile, France

    Nicolas Burdin, Bruno Guy &  Philippe Moingeon

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  1. Nicolas Burdin
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Correspondence to Philippe Moingeon.

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Burdin, N., Guy, B. & Moingeon, P. Immunological Foundations to the Quest for New Vaccine Adjuvants. BioDrugs 18, 79–93 (2004). https://doi.org/10.2165/00063030-200418020-00002

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