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Impfung gegen Tuberkulose

Zeit, an die nächste Impfstoffgeneration zu denken

Vaccination against tuberculosis

Time to think about the next generation vaccinations

  • Leitthema
  • Published:
Der Pneumologe Aims and scope

Zusammenfassung

Bemühungen der vergangenen zwei Jahrzehnte haben dazu geführt, dass sich eine Fülle von Tuberkulose(TB)-Impfstoffen in der Erforschung und Entwicklung befindet. Zwar hat noch keine Vakzine alle klinischen Studien erfolgreich durchlaufen, viele befinden sich aber in der fortgeschrittenen klinischen Prüfung. Diese Impfstoffe zielen auf die Prävention der aktiven TB ab. Die Mehrheit ist dabei für den Einsatz vor TB-Exposition gedacht, in jüngerer Zeit sind aber auch Vertreter für einen Zeitpunkt nach der Exposition oder zur Mehrphasenapplikation hinzugekommen. Auch einige therapeutische Impfstoffe befinden sich in der klinischen Testung. Die Präexpositionsimpfung mit der zugelassenen TB-Vakzine BCG (Bacillus Calmette-Guérin) verhindert schwere TB-Formen bei Kindern, nicht aber bei Jugendlichen und Erwachsenen. Die gegenwärtigen Ansätze der Impfstoffentwicklung umfassen keine Strategien zur Vermeidung oder Beseitigung einer Infektion mit dem Erreger Mycobacterium tuberculosis (Mtb). Im besten Fall sind sie BCG quantitativ überlegen in Bezug auf die Prävention einer aktiven TB über längere Zeitspannen – mit Blick auf die latente Mtb-Infektion idealerweise auf Lebenszeit. Mit qualitativ verbesserten Impfstoffen sollte die Prävention oder Beseitigung der Mtb-Infektion möglich sein. So ließe sich auch die Gefahr der TB-Reaktivierung bannen. Zur Erreichung dieses Ziels ist es nun an der Zeit, an grundlegend neue Strategien zu denken.

Abstract

Efforts over the last two decades have led to a rich research and development pipeline of tuberculosis (TB) vaccines. Although none of the candidates has so far successfully completed the clinical trial pipeline, many are in advanced stages of clinical assessment. These vaccines aim at prevention of active TB with most being considered for pre-exposure with recent additions for postexposure or multistage administration. Some therapeutic vaccines are also in the stage of clinical assessment. Preexposure vaccination with the licensed TB vaccine BCG (Bacillus Calmette-Guérin) prevents severe forms of TB in children but not in adolescents and adults. The current vaccine pipeline does not include strategies which prevent or eliminate infection with the causative agent Mycobacterium tuberculosis (Mtb). In a best-case scenario they are quantitatively superior to BCG in preventing active TB over prolonged periods of time, ideally lifelong in the face of latent Mtb infections. Qualitatively superior vaccines should be capable of preventing or eliminating Mtb infections and in this way eliminate the risk of TB reactivation. The time is now ripe to exploit radically new strategies to achieve this goal.

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Abbreviations

Ad35:

Adenovirus 35

AS:

Adjuvantes System

Ag85A:

Antigen 85A

BCG:

Bacillus Calmette-Guérin

DTH:

Überempfindlichkeit vom Spättyp

DC:

Dendritische Zellen

GLA:

Glucopyranosyllipid A

IFN-γ:

Interferon-γ

IGRA:

IFN-γ-release-Assays

IL:

Interleukin

LTBI:

Latente Mtb-Infektion

Hly:

Listeriolysin

MHC:

Haupthistokompatibilitätskomplex

MP:

Mononukleäre Phagozyten

MAIT:

„mucosal-associated invariant T cells“

MIP:

Mycobacterium indicus pranii

Mtb:

Mycobacterium tuberculosis

NK:

Natürliche Killerzellen

Pfo:

Perfringolysin

P:

Prolin

E:

Glutamat

S:

Serin

T:

Threonin = PEST

Treg-Zellen:

Regulatorische T-Zellen

TLR:

„toll-like receptor“

TDB:

Trehalose-6,6′-dibehenat

TB:

Tuberkulose

TST:

Tuberkulinhauttest

TNF:

Tumor-Nekrose-Faktor

Th1:

Typ-1-Helferzellen

UreC:

Urease C

Literatur

  1. Cooper AM (2009) Cell-mediated immune responses in tuberculosis. Annu Rev Immunol 27:393–422

    Article  CAS  PubMed  Google Scholar 

  2. Rohde K, Yates RM, Purdy GE, Russell DG (2007) Mycobacterium tuberculosis and the environment within the phagosome. Immunol Rev 219:37–54

    Article  CAS  PubMed  Google Scholar 

  3. Sturgill-Koszycki S, Schlesinger PH, Chakraborty P et al (1994) Lack of acidification in Mycobacterium phagosomes produced by exclusion of the vesicular proton-ATPase. Science 263:678–681

    Article  CAS  PubMed  Google Scholar 

  4. Barry CE III, Boshoff HI, Dartois V et al (2009) The spectrum of latent tuberculosis: rethinking the biology and intervention strategies. Nat Rev Microbiol 7:845–855

    CAS  PubMed  Google Scholar 

  5. Esmail H, Barry CE III, Wilkinson RJ (2012) Understanding latent tuberculosis: the key to improved diagnostic and novel treatment strategies. Drug Discov Today 17:514–521

    Article  PubMed Central  PubMed  Google Scholar 

  6. Gengenbacher M, Kaufmann SH (2012) Mycobacterium tuberculosis: success through dormancy. FEMS Microbiol Rev 36:514–532

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Young DB, Gideon HP, Wilkinson RJ (2009) Eliminating latent tuberculosis. Trends Microbiol 17(5):183–188

    Article  CAS  PubMed  Google Scholar 

  8. Betts JC, Lukey PT, Robb LC et al (2002) Evaluation of a nutrient starvation model of Mycobacterium tuberculosis persistence by gene and protein expression profiling. Mol Microbiol 43:717–731

    Article  CAS  PubMed  Google Scholar 

  9. Schnappinger D, Ehrt S, Voskuil MI et al (2003) Transcriptional adaptation of Mycobacterium tuberculosis within macrophages: insights into the phagosomal environment. J Exp Med 198:693–704

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Chao MC, Rubin EJ (2010) Letting sleeping dos lie: does dormancy play a role in tuberculosis? Annu Rev Microbiol 64:293–311

    Article  CAS  PubMed  Google Scholar 

  11. Kaufmann SH (2011) Fact and fiction in tuberculosis vaccine research: 10 years later. Lancet Infect Dis 11:633–640

    Article  PubMed  Google Scholar 

  12. Kaufmann SH (2011) Tuberculosis vaccines-a new kid on the block. Nat Med 17:159–160

    Article  CAS  PubMed  Google Scholar 

  13. Kaufmann SH (2012) Tuberculosis vaccine development: strength lies in tenacity. Trends Immunol 33:373–379

    Article  CAS  PubMed  Google Scholar 

  14. Bertholet S, Ireton GC, Ordway DJ et al (2010) A defined tuberculosis vaccine candidate boosts BCG and protects against multidrug-resistant Mycobacterium tuberculosis. Sci Transl Med 2:53ra74

    Article  PubMed Central  PubMed  Google Scholar 

  15. Aagaard C, Hoang T, Dietrich J et al (2011) A multistage tuberculosis vaccine that confers efficient protection pre- and post-exposure. Nat Med 17:189–194

    Article  CAS  PubMed  Google Scholar 

  16. Dorhoi A, Kaufmann SH (2009) Fine-tuning of T cell responses during infection. Curr Opin Immunol 21:367–377

    Article  CAS  PubMed  Google Scholar 

  17. Reece ST, Kaufmann SH (2012) Floating between the poles of pathology and protection: can we pin down the granuloma in tuberculosis? Curr Opin Microbiol 15:63–70

    Article  PubMed  Google Scholar 

  18. Dorhoi A, Reece ST, Kaufmann SHE (2012) Immunity to intracellular bacteria. In: Paul WE (Hrsg) Fundamental immunology, 7. Aufl. Wolters Kluwer Health, Philadelphia, S 973–1000

  19. Ottenhoff TH, Lewinsohn DALDM (2008) Human CD4 and CD8 T cell responses to Mycobacterium tuberculosis: antigen specificity, function, implications and applications. In: Kaufmann SHE, Britton WJ (Hrsg) Handbook of tuberculosis: immunology and cell biology. Wiley-VCH, Weinheim, S 119–156

  20. Khader SA, Bell GK, Pearl JE et al (2007) IL-23 and IL-17 in the establishment of protective pulmonary CD4(+) T cell responses after vaccination and during Mycobacterium tuberculosis challenge. Nat Immunol 8:369–377

    Article  CAS  PubMed  Google Scholar 

  21. Desel C, Dorhoi A, Bandermann S et al (2011) Recombinant BCG {Delta}ureC hly+ induces superior protection over parental BCG by stimulating a balanced combination of type 1 and type 17 cytokine responses. J Infect Dis 204:1573–1584

    Article  CAS  PubMed  Google Scholar 

  22. Cruz A, Fraga AG, Fountain JJ et al (2010) Pathological role of interleukin 17 in mice subjected to repeated BCG vaccination after infection with Mycobacterium tuberculosis. J Exp Med 207:1609–1616

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Auffray C, Sieweke MH, Geissmann F (2009) Blood monocytes: development, heterogeneity, and relationship with dendritic cells. Annu Rev Immunol 27:669–692

    Article  CAS  PubMed  Google Scholar 

  24. Chowdhury D, Lieberman J (2008) Death by a thousand cuts: granzyme pathways of programmed cell death. Annu Rev Immunol 26:389–420

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Nathan C (2006) Neutrophils and immunity: challenges and opportunities. Nat Rev Immunol 6:173–182

    Article  CAS  PubMed  Google Scholar 

  26. Kaufmann SH (2010) Future vaccination strategies against tuberculosis: thinking outside the box. Immunity 33:567–577

    Article  CAS  PubMed  Google Scholar 

  27. Mosmann TR, Coffman RL (1989) TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol 7:145–173

    Article  CAS  PubMed  Google Scholar 

  28. Romagnani S (2005) Cytokines. In: Kaufmann SHE, Steward MW (Hrsg) Immunology, 10. Aufl. Hodder Arnold, London. S 273–299

  29. Harding CV, Boom WH (2010) Regulation of antigen presentation by Mycobacterium tuberculosis: a role for Toll-like receptors. Nat Rev Microbiol 8:296–307

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Kaufmann SHE (2003) Immunity to intracellular bacteria. In: Paul WE (Hrsg) Fundamental immunology, 5. Aufll. Lippincott-Raven, Philadelphia, S 1229–1261

  31. Stenger S, Hanson DA, Teitelbaum R et al (1998) An antimicrobial activity of cytolytic T cells mediated by granulysin. Science 282:121–125

    Article  CAS  PubMed  Google Scholar 

  32. Wel N van der, Hava D, Houben D et al (2007) M. tuberculosis and M. leprae translocate from the phagolysosome to the cytosol in myeloid cells. Cell 129:1287–1298

    Article  PubMed  Google Scholar 

  33. Schaible UE, Winau F, Sieling PA et al (2003) Apoptosis facilitates antigen presentation to T lymphocytes through MHC-I and CD1 in tuberculosis. Nat Med 9:1039–1046

    Article  CAS  PubMed  Google Scholar 

  34. Winau F, Weber S, Sad S et al (2006) Apoptotic vesicles crossprime CD8 T cells and protect against tuberculosis. Immunity 24:105–117

    Article  CAS  PubMed  Google Scholar 

  35. Joosten SA, Ottenhoff TH (2008) Human CD4 and CD8 regulatory T cells in infectious diseases and vaccination. Hum Immunol 69:760–770

    Article  CAS  PubMed  Google Scholar 

  36. Urdahl KB, Shafiani S, Ernst JD (2011) Initiation and regulation of T-cell responses in tuberculosis. Mucosal Immunol 4:288–293

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Keir ME, Butte MJ, Freeman GJ, Sharpe AH (2008) PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol 26:677–704

    Article  CAS  PubMed  Google Scholar 

  38. WHO (2011) Global Tuberculosis Control 2011. World Health Organization, Geneva

  39. Harries AD, Zachariah R, Corbett EL et al (2010) The HIV-associated tuberculosis epidemic – when will we act? Lancet 375:1906–1919

    Article  PubMed  Google Scholar 

  40. Lawn SD, Zumla AI (2011) Tuberculosis. Lancet 378:57–72

    Article  PubMed  Google Scholar 

  41. Ulrichs T, Kaufmann SHE (2006) New insights into the function of granulomas in human tuberculosis. J Pathol 208:261–269

    Article  CAS  PubMed  Google Scholar 

  42. Calmette A, Guérin C, Boquet A, Négre L (1927) La vaccination préventive contre la tuberculose par le „BCG“. Masson, Paris

  43. Kaufmann SH, Hussey G, Lambert PH (2010) New vaccines for tuberculosis. Lancet 375:2110–2119

    Article  PubMed  Google Scholar 

  44. Colditz GA, Brewer TF, Berkey CS et al (1994) Efficacy of BCG vaccine in the prevention of tuberculosis. Meta-analysis of the published literature. JAMA 271:698–702

    Article  CAS  PubMed  Google Scholar 

  45. Kaufmann SH, Gengenbacher M (2012) Recombinant live vaccine candidates against tuberculosis. Curr Opin Biotechnol 23:900–907

    Article  CAS  PubMed  Google Scholar 

  46. Abou-Zeid C, Ratliff TL, Wiker HG et al (1988) Characterization of fibronectin-binding antigens released by Mycobacterium tuberculosis and Mycobacterium bovis BCG. Infect Immun 56:3046–3051

    CAS  PubMed Central  PubMed  Google Scholar 

  47. Belisle JT, Vissa VD, Sievert T et al (1997) Role of the major antigen of Mycobacterium tuberculosis in cell wall biogenesis. Science 276:1420–1422

    Article  CAS  PubMed  Google Scholar 

  48. Horwitz MA, Harth G, Dillon BJ, Maslesa-Galic S (2000) Recombinant bacillus Calmette-Guerin (BCG) vaccines expressing the Mycobacterium tuberculosis 30-kDa major secretory protein induce greater protective immunity against tuberculosis than conventional BCG vaccines in a highly susceptible animal model. Proc Natl Acad Sci U S A 97:13853–13858

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  49. Grode L, Seiler P, Baumann S et al (2005) Increased vaccine efficacy against tuberculosis of recombinant Mycobacterium bovis bacille Calmette-Guérin mutants that secrete listeriolysin. J Clin Invest 115:2472–2479

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  50. Bavdek A, Kostanjsek R, Antonini V et al (2012) pH dependence of listeriolysin O aggregation and pore-forming ability. FEBS J 279:126–141

    Article  CAS  PubMed  Google Scholar 

  51. Farinacci M, Weber S, Kaufmann SHE (2012) The recombinant tuberculosis vaccine rBCG ΔureC::hly+ induces apoptotic vescicles for improved priming of CD4+ and CD8+ T cells. Vaccine 30:7614

    Article  Google Scholar 

  52. Decatur AL, Portnoy DA (2000) A PEST-like sequence in listeriolysin O essential for Listeria monocytogenes pathogenicity. Science 290:992–995

    Article  CAS  PubMed  Google Scholar 

  53. Palmer M (2001) The family of thiol-activated, cholesterol-binding cytolysins. Toxicon 39:1681–1689

    Article  CAS  PubMed  Google Scholar 

  54. Sun R, Skeiky YA, Izzo A et al (2009) Novel recombinant BCG expressing perfringolysin O and the over-expression of key immunodominant antigens; pre-clinical characterization, safety and protection against challenge with Mycobacterium tuberculosis. Vaccine 27:4412–4423

    Article  CAS  PubMed  Google Scholar 

  55. Mollenkopf HJ, Grode L, Mattow J et al (2004) Application of mycobacterial proteomics to vaccine design: improved protection by Mycobacterium bovis BCG prime-Rv3407 DNA boost vaccination against tuberculosis. Infect Immun 72:6471–6479

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  56. Kupferschmidt K (2011) Infectious disease. Taking a new shot at a TB vaccine. Science 334:1488–1490

    Article  PubMed  Google Scholar 

  57. Arbues A, Aguilo JI, Gonzalo-Asensio J et al (2013) Construction, characterization and preclinical evaluation of MTBVAC, the first live-attenuated M. tuberculosis-based vaccine to enter clinical trials. Vaccine 31:4867–4873

    Article  CAS  PubMed  Google Scholar 

  58. Von Eschen K, Morrison R, Braun M et al (2009) The candidate tuberculosis vaccine Mtb72F/AS02A: tolerability and immunogenicity in humans. Hum Vaccin 5:475–482

    Google Scholar 

  59. Simeone R, Bottai D, Brosch R (2009) ESX/type VII secretion systems and their role in host-pathogen interaction. Curr Opin Microbiol 12:4–10

    Article  CAS  PubMed  Google Scholar 

  60. Skjot RL, Brock I, Arend SM et al (2002) Epitope mapping of the immunodominant antigen TB10.4 and the two homologous proteins TB10.3 and TB12.9, which constitute a subfamily of the esat-6 gene family. Infect Immun 70:5446–5453

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  61. Diel R, Goletti D, Ferrara G et al (2011) Interferon-gamma release assays for the diagnosis of latent Mycobacterium tuberculosis infection: a systematic review and meta-analysis. Eur Respir J 37:88–99

    Article  CAS  PubMed  Google Scholar 

  62. Dietrich J, Aagaard C, Leah R et al (2005) Exchanging ESAT6 with TB10.4 in an Ag85B fusion molecule-based tuberculosis subunit vaccine: efficient protection and ESAT6-based sensitive monitoring of vaccine efficacy. J Immunol 174:6332–6339

    CAS  PubMed  Google Scholar 

  63. Lingnau K, Riedl K, Gabain A von (2007) IC31 and IC30, novel types of vaccine adjuvant based on peptide delivery systems. Expert Rev Vaccines 6:741–746

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed Central  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  66. McShane H, Pathan AA, Sander CR et al (2004) Recombinant modified vaccinia virus Ankara expressing antigen 85A boosts BCG-primed and naturally acquired antimycobacterial immunity in humans. Nat Med 10:1240–1244

    Article  CAS  PubMed  Google Scholar 

  67. Tameris MD, Hatherill M, Landry BS et al (2013) Safety and efficacy of MVA85A, a new tuberculosis vaccine, in infants previously vaccinated with BCG: a randomised, placebo-controlled phase 2b trial. Lancet. doi:10.1016/S0140-6736(13)60177-4

  68. Radosevic K, Wieland CW, Rodriguez A et al (2007) Protective immune responses to a recombinant adenovirus type 35 tuberculosis vaccine in two mouse strains: CD4 and CD8 T-cell epitope mapping and role of gamma interferon. Infect Immun 75:4105–4115

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  69. Santosuosso M, McCormick S, Zhang X et al (2006) Intranasal boosting with an adenovirus-vectored vaccine markedly enhances protection by parenteral Mycobacterium bovis BCG immunization against pulmonary tuberculosis. Infect Immun 74:4634–4643

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  70. Lin PL, Dietrich J, Tan E et al (2012) The multistage vaccine H56 boosts the effects of BCG to protect cynomolgus macaques against active tuberculosis and reactivation of latent Mycobacterium tuberculosis infection. J Clin Invest 122:303–314

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  71. Von Reyn CF, Mtei L, Arbeit R et al (2010) Prevention of tuberculosis in Bacille Calmette-Guérin-primed, HIV-infected adults boosted with an inactivated whole-cell mycobacterial vaccine. Aids 24:675–685

    Article  Google Scholar 

  72. Yang XY, Chen QF, Li YP, Wu SM (2011) Mycobacterium vaccae as adjuvant therapy to anti-tuberculosis chemotherapy in never-treated tuberculosis patients: a meta-analysis. PLoS One 6:e23826

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  73. Gupta A, Ahmad FJ, Ahmad F et al (2012) Efficacy of Mycobacterium indicus pranii immunotherapy as an adjunct to chemotherapy for tuberculosis and underlying immune responses in the lung. PLoS One 7:e39215

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  74. Cardona PJ (2006) RUTI: a new chance to shorten the treatment of latent tuberculosis infection. Tuberculosis (Edinb) 86:273–289

    Google Scholar 

  75. Vilaplana C, Montane E, Pinto S et al (2009) Double-blind, randomized, placebo-controlled Phase I Clinical Trial of the therapeutical antituberculous vaccine RUTI(®). Vaccine 28:1106–1116

    Article  PubMed  Google Scholar 

  76. Keane J, Gershon S, Wise RP et al (2001) Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N Engl J Med 345:1098–1104

    Article  CAS  PubMed  Google Scholar 

  77. Casadevall A, Pirofski LA (2012) A new synthesis for antibody-mediated immunity. Nat Immunol 13:21–28

    Article  CAS  Google Scholar 

  78. Maglione PJ, Chan J (2009) How B cells shape the immune response against Mycobacterium tuberculosis. Eur J Immunol 39:676–686

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  79. Manz RA, Hauser AE, Hiepe F, Radbruch A (2005) Maintenance of serum antibody levels. Annu Rev Immunol 23:367–386

    Article  CAS  PubMed  Google Scholar 

  80. Amulic B, Cazalet C, Hayes GL et al (2012) Neutrophil function: from mechanisms to disease. Annu Rev Immunol 30:459–489

    Article  CAS  PubMed  Google Scholar 

  81. Di Santo JP (2006) Natural killer cell developmental pathways: a question of balance. Annu Rev Immunol 24:257–286

    Article  Google Scholar 

  82. Dorhoi A, Reece ST, Kaufmann SH (2011) For better or for worse: the immune response against Mycobacterium tuberculosis balances pathology and protection. Immunol Rev 240:235–251

    Article  CAS  PubMed  Google Scholar 

  83. Mizgerd JP (2006) Lung infection – a public health priority. PLoS Med 3:e76

    Article  PubMed Central  PubMed  Google Scholar 

  84. Doerschuk CM (2001) Mechanisms of leukocyte sequestration in inflamed lungs. Microcirculation 8:71–88

    CAS  PubMed  Google Scholar 

  85. Soysal A, Millington KA, Bakir M et al (2005) Effect of BCG vaccination on risk of Mycobacterium tuberculosis infection in children with household tuberculosis contact: a prospective community-based study. Lancet 366:1443–1451

    Article  PubMed  Google Scholar 

  86. Maertzdorf J, Weiner IJ, Kaufmann SH (2012) Enabling biomarkers for tuberculosis control. Int J Tuberc Lung Dis 16:1140–1148

    Article  CAS  PubMed  Google Scholar 

  87. Weiner J III, Maertzdorf J, Kaufmann SH (2012) The dual role of biomarkers for understanding basic principles and devising novel intervention strategies in tuberculosis. Ann N Y Acad Sci 1283:22–29

    Article  PubMed  Google Scholar 

  88. Rappuoli R, Aderem A (2011) A 2020 vision for vaccines against HIV, tuberculosis and malaria. Nature 473:463–469

    Article  CAS  PubMed  Google Scholar 

  89. Querec TD, Akondy RS, Lee EK et al (2009) Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans. Nat Immunol 10:116–125

    Article  CAS  PubMed  Google Scholar 

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Danksagungen

Ich danke M.L. Grossman für die Unterstützung bei der Vorbereitung des Manuskripts und D. Schad für die Hilfe bei der Erstellung der Grafiken. Die Arbeit an der Entwicklung von Impfstoffen und Biomarkern in meinem Labor wird im Rahmen der EU-FP7-Projekte NEWTBVAC (Health-F3-2009-241745) und TRANSVAC (FP7-INFRASTRUCTURES-2008-228403) von der Europäischen Union unterstützt und zudem im Bill & Melinda Gates Foundation Grand Challenge Program GC6-74 (BMGF Nr. 37772), in den European-and-Developing-Countries-Clinical-Trials-Partnership(EDCTP)-Projekten „African European Tuberculosis Consortium“ (AE-TBC) und „Collaboration and integration of tuberculosis vaccine trials in Europe and Africa“ (TBTEA), im EU-FP7-Projekt ADITEC (HEALTH-F4-2011-280873) und im Rahmen des Projekts „Biomarkers for Enhanced Vaccine Safety“ (BioVacSafe) des gemeinschaftlichen Unternehmens IMI (IMI JU Grant Nr. 115308).

Einhaltung ethischer Richtlinien

Interessenkonflikt. S.H.E. Kaufmann ist Miterfinder des rBCG-Impfstoffs VPM1002 (rBCGΔureC::hly) sowie Mitglied der wissenschaftlichen Beiräte von Vakzine Projekt Management GmbH und Aeras. Er war Mitglied des wissenschaftlichen Beirats von Intercell AG.

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  1. Abteilung für Immunologie, Max-Planck-Institut für Infektionsbiologie, Charitéplatz 1, 10117, Berlin, Deutschland

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Beitrag erscheint als gekürzte Übernahme des Originalartikels mit freundlicher Genehmigung von Elsevier: Kaufmann SHE (2013) Tuberculosis vaccines: time to think about the next generation. Sem Immunol 25:172–181

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Kaufmann, S. Impfung gegen Tuberkulose. Pneumologe 11, 42–52 (2014). https://doi.org/10.1007/s10405-013-0697-0

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