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01-04-2013 | Review

Targeting multidrug-resistant tuberculosis (MDR-TB) by therapeutic vaccines

Authors: Satria A. Prabowo, Matthias I. Gröschel, Ed D. L. Schmidt, Alena Skrahina, Traian Mihaescu, Serap Hastürk, Rotislav Mitrofanov, Edita Pimkina, Ildikó Visontai, Bouke de Jong, John L. Stanford, Père-Joan Cardona, Stefan H. E. Kaufmann, Tjip S. van der Werf

Published in: Medical Microbiology and Immunology | Issue 2/2013

Abstract

Tuberculosis (TB) has scourged humankind for millennia, and latent infection affects nearly one-third of today’s world population. The emergence of multidrug-resistant (MDR)-TB is a major global threat and reflects treatment failure of drug-sensitive disease. MDR-TB management is a burden for patients and society; success rates are unacceptably low with prolonged treatment duration. Mycobacterium tuberculosis (Mtb) possesses the ability to transform into a dormant state in which it can persist in the face of antimicrobial treatment and host defense. This sub-population of persisters is largely responsible for lengthy and difficult treatment. Targeting persistent bacilli could eventually improve the treatment success rate (currently 50–65 %) and shorten duration of treatment. A subset of therapies in the pipeline, termed therapeutic vaccines, use the host immune response to attack Mtb. The historical occurrence of an exacerbated host response has resulted in a negative perception of therapeutic vaccines. Thus, a renewed concept of immunotherapy is needed. We review current perspectives of immunotherapy in MDR-TB based on the knowledge of TB immunology and briefly discuss the profiles of several therapeutic vaccine products.

Keshavjee S, Farmer PE (2012) Tuberculosis, drug resistance, and the history of modern medicine. N Engl J Med 367(10):931–936PubMedCrossRef

Frieden TR, Sterling T, Pablos-Mendez A, Kilburn JO, Cauthen GM, Dooley SW (1993) The emergence of drug-resistant tuberculosis in New York City. N Engl J Med 328(8):521–526PubMedCrossRef

Edlin BR, Tokars JI, Grieco MH, Crawford JT, Williams J, Sordillo EM, Ong KR, Kilburn JO, Dooley SW, Castro KG (1992) An outbreak of multidrug-resistant tuberculosis among hospitalized patients with the acquired immunodeficiency syndrome. N Engl J Med 326(23):1514–1521PubMedCrossRef

World Health Organization (1994) Tuberculosis: a global emergency. WHO, Geneva

Raviglione M, Marais B, Floyd K et al (2012) Scaling up interventions to achieve global tuberculosis control: progress and new developments. Lancet 379(9829):1902–1913PubMedCrossRef

Swaminathan S, Ramachandran R, Baskaran G, Paramasivan CN, Ramanathan U, Venkatesan P, Prabhakar R, Datta M (2000) Risk of development of tuberculosis in HIV-infected patients. Int J Tuberc Lung Dis 4(9):839–844PubMed

World Health Organization (2011) Global tuberculosis control. WHO, Geneva

Nathanson E, Nunn P, Uplekar M, Floyd K, Jaramillo E, Lönnroth K, Weil D, Raviglione M (2010) MDR tuberculosis—critical steps for prevention and control. N Engl J Med 363(11):1050–1058PubMedCrossRef

Skrahina A, Hurevich H, Zalutskaya A, Sahalchyk E, Astrauko A, van Gemert W, Hoffner S, Rusovich V, Zignol M (2012) Alarming levels of drug-resistant tuberculosis in Belarus: results of a survey in Minsk. Eur Respir J 39(6):1425–1431PubMedCrossRef

10.

World Health Organization (2010) Multidrug and extensively drug-resistant TB (M/XDR TB)—Global Report on Surveillance and Response 2010. WHO, Geneva

11.

Gandhi NR, Moll A, Sturm AW, Pawinski R, Govender T, Lalloo U, Zeller K, Andrews J, Friedland G (2006) Extensively drug-resistant tuberculosis as a cause of death in patients co-infected with tuberculosis and HIV in a rural area of South Africa. Lancet 368(9547):1575–1580PubMedCrossRef

12.

Zhao Y, Xu S, Wang L et al (2012) National survey of drug-resistant tuberculosis in China. N Engl J Med 366(23):2161–2170PubMedCrossRef

13.

Liang L, Wu Q, Gao L et al (2012) Factors contributing to the high prevalence of multidrug-resistant tuberculosis: a study from China. Thorax 67(7):632–638PubMedCrossRef

14.

Olson EN (2004) Undermining the endothelium by ablation of MAPK-MEF2 signaling. J Clin Invest 113(8):1110–1112PubMed

15.

Chaisson RE, Nuermberger EL (2012) Confronting multidrug-resistant tuberculosis. N Engl J Med 366(23):2223–2224PubMedCrossRef

16.

Ahuja SD, Ashkin D, Avendano M et al (2012) Multidrug resistant pulmonary tuberculosis treatment regimens and patient outcomes: an individual patient data meta-analysis of 9,153 patients. PLoS Med 9(8):e1001300PubMedCrossRef

17.

Diel R, Rutz S, Castell S, Schaberg T (2012) Cost of illness of tuberculosis in Germany. Eur Respir J 40(1):143–151PubMedCrossRef

18.

Orenstein EW, Basu S, Shah NS, Andrews JR, Friedland GH, Moll AP, Gandhi NR, Galvani AP (2009) Treatment outcomes among patients with multidrug-resistant tuberculosis: systematic review and meta-analysis. Lancet Infect Dis 9(3):153–161PubMedCrossRef

19.

Yew WW, Lange C, Leung CC (2011) Treatment of tuberculosis: update 2010. Eur Respir J 37(2):441–462PubMedCrossRef

20.

Leimane V, Dravniece G, Riekstina V, Sture I, Kammerer S, Chen MP, Skenders G, Holtz TH (2010) Treatment outcome of multidrug/extensively drug-resistant tuberculosis in Latvia, 2000–2004. Eur Respir J 36(3):584–593PubMedCrossRef

21.

Migliori GB, De Iaco G, Besozzi G, Centis R, Cirillo DM (2007) First tuberculosis cases in Italy resistant to all tested drugs. Euro Surveill Eur Commun Dis Bull 12(5):E070517.1

22.

Velayati AA, Masjedi MR, Farnia P, Tabarsi P, Ghanavi J, ZiaZarifi AH, Hoffner SE (2009) Emergence of new forms of totally drug-resistant Tuberculosis Bacilli: super extensively drug-resistant tuberculosis or totally drug-resistant strains in Iran. Chest 136(2):420–425PubMedCrossRef

23.

Udwadia ZF, Amale RA, Ajbani KK, Rodrigues C (2012) Totally drug-resistant tuberculosis in India. Clin Infect Dis 54(4):579–581PubMedCrossRef

24.

Chang KC, Leung CC, Grosset J, Yew WW (2011) Treatment of tuberculosis and optimal dosing schedules. Thorax 66(11):997–1007PubMedCrossRef

25.

Faustini A (2006) Risk factors for multidrug resistant tuberculosis in Europe: a systematic review. Thorax 61(2):158–163PubMedCrossRef

26.

Pasipanodya JG, Srivastava S, Gumbo T (2012) Meta-analysis of clinical studies supports the pharmacokinetic variability hypothesis for acquired drug resistance and failure of antituberculosis therapy. Clin Infect Dis 55(2):169–177PubMedCrossRef

27.

Axelsson-Robertson R, Magalhaes I, Parida SK, Zumla A, Maeurer M (2012) The Immunological footprint of Mycobacterium tuberculosis T-cell epitope recognition. J Infect Dis 205(suppl 2):S301–S315PubMedCrossRef

28.

Gupta A, Kaul A, Tsolaki AG, Kishore U, Bhakta S (2012) Mycobacterium tuberculosis: immune evasion, latency and reactivation. Immunobiology 217(3):363–374PubMedCrossRef

29.

van Altena R, Duggirala S, Gröschel MIP, van der Werf TS (2011) Immunology in tuberculosis: challenges in monitoring of disease activity and identifying correlates of protection. Curr Pharm Des 17(27):2853–2862PubMedCrossRef

30.

Kleinnijenhuis J, Oosting M, Joosten LAB, Netea MG, van Crevel R (2011) Innate immune recognition of Mycobacterium tuberculosis. Clin Dev Immunol 2011:1–12CrossRef

31.

Dheda K, Schwander SK, Zhu B, van Zyl-Smit RN, Zhang Y (2010) The immunology of tuberculosis: from bench to bedside. Respirology 15(3):433–450PubMedCrossRef

32.

Fabri M, Stenger S, Shin D-M et al (2011) Vitamin D is required for IFN-gamma-mediated antimicrobial activity of human macrophages. Sci Transl Med 3(104):104ra102PubMedCrossRef

33.

Schaible UE, Sturgill-Koszycki S, Schlesinger PH, Russell DG (1998) Cytokine activation leads to acidification and increases maturation of Mycobacterium avium-containing phagosomes in murine macrophages. J Immunol 160(3):1290–1296PubMed

34.

Liu PT, Modlin RL (2008) Human macrophage host defense against Mycobacterium tuberculosis. Curr Opin Immunol 20(4):371–376PubMedCrossRef

35.

Welin A, Lerm M (2012) Inside or outside the phagosome? The controversy of the intracellular localization of Mycobacterium tuberculosis. Tuberc (Edinb) 92(2):113–120CrossRef

36.

Rohde KH, Abramovitch RB, Russell DG (2007) Mycobacterium tuberculosis invasion of macrophages: linking bacterial gene expression to environmental cues. Cell Host Microbe 2(5):352–364PubMedCrossRef

37.

Russell DG (2001) Mycobacterium tuberculosis: here today, and here tomorrow. Nat Rev Mol Cell Biol 2(8):569–577PubMedCrossRef

38.

Melo RCN, Dvorak AM (2012) Lipid body–phagosome interaction in macrophages during infectious diseases: host defense or pathogen survival strategy? PLoS Pathog 8(7):e1002729PubMedCrossRef

39.

Peyron P, Vaubourgeix J, Poquet Y et al (2008) Foamy macrophages from tuberculous patients’ granulomas constitute a nutrient-rich reservoir for M. tuberculosis persistence. PLoS Pathog 4(11):e1000204PubMedCrossRef

40.

Pandey AK, Sassetti CM (2008) Mycobacterial persistence requires the utilization of host cholesterol. Proc Natl Acad Sci USA 105(11):4376–4380PubMedCrossRef

41.

Colombo MI, Beron W, Stahl PD (1997) Calmodulin regulates endosome fusion. J Biol Chem 272(12):7707–7712PubMedCrossRef

42.

Maniak M, Rauchenberger R, Albrecht R, Murphy J, Gerisch G (1995) Coronin involved in phagocytosis: dynamics of particle-induced relocalization visualized by a green fluorescent protein Tag. Cell 83(6):915–924PubMedCrossRef

43.

Flynn JL, Chan J, Triebold KJ, Dalton DK, Stewart TA, Bloom BR (1993) An essential role for interferon gamma in resistance to Mycobacterium tuberculosis infection. J Exp Med 178(6):2249–2254PubMedCrossRef

44.

Kaufmann SHE (2010) Novel tuberculosis vaccination strategies based on understanding the immune response. J Int Med 267(4):337–353CrossRef

45.

Herbst S, Schaible UE, Schneider BE (2011) Interferon gamma activated macrophages kill mycobacteria by nitric oxide induced apoptosis. PLoS ONE 6(5):e19105PubMedCrossRef

46.

Ní Cheallaigh C, Keane J, Lavelle EC, Hope JC, Harris J (2011) Autophagy in the immune response to tuberculosis: clinical perspectives. Clin Exp Immunol 164(3):291–300PubMedCrossRef

47.

Hanekom WA, Dockrell HM, Ottenhoff THM, Doherty TM, Fletcher H, McShane H, Weichold FF, Hoft DF, Parida SK, Fruth UJ (2008) Immunological outcomes of new tuberculosis vaccine trials: WHO panel recommendations. PLoS Med 5(7):e145PubMedCrossRef

48.

Rook GAW, Hernández-Pando R, Dheda K, Teng Seah G (2004) IL-4 in tuberculosis: implications for vaccine design. Trends Immunol 25(9):483–488PubMedCrossRef

49.

VanHeyningen TK, Collins HL, Russell DG (2001) IL-6 produced by macrophages infected with Mycobacterium species suppresses T cell responses. J Immunol 158(1):330–337

50.

Hett EC, Rubin EJ (2008) Bacterial growth and cell division: a mycobacterial perspective. Microbiol Mol Biol Rev 72(1):126–156PubMedCrossRef

51.

Cardona P-J (2006) RUTI: a new chance to shorten the treatment of latent tuberculosis infection. Tuberc (Edinb) 86(3–4):273–289CrossRef

52.

Gengenbacher M, Kaufmann SHE (2012) Mycobacterium tuberculosis: success through dormancy. FEMS Microbiol Rev 36(3):514–532PubMedCrossRef

53.

Zhang Y, Yew WW, Barer MR (2012) Targeting persisters for tuberculosis control. Antimicrob Agents Chemother 56(5):2223–2230PubMedCrossRef

54.

Cardona P-J (2010) Revisiting the natural history of tuberculosis. Arch Immunol Ther Exp (Warsz) 58(1):7–14CrossRef

55.

Barry CE, Boshoff HI, Dartois V, Dick T, Ehrt S, Flynn J, Schnappinger D, Wilkinson RJ, Young D (2009) The spectrum of latent tuberculosis: rethinking the biology and intervention strategies. Nat Rev Microbiol 7(12):845–855PubMed

56.

Locht C, Rouanet C, Hougardy J-M, Mascart F (2007) How a different look at latency can help to develop novel diagnostics and vaccines against tuberculosis. Expert Opin Biol Ther 7(11):1665–1677PubMedCrossRef

57.

Neyrolles O, Hernández-Pando R, Pietri-Rouxel F et al (2006) Is adipose tissue a place for Mycobacterium tuberculosis persistence? PLoS ONE 1(1):e43PubMedCrossRef

58.

Hernandez-Pando R, Jeyanathan M, Mengistu G, Aguilar D, Orozco H, Harboe M, Rook GA, Bjune G (2000) Persistence of DNA from Mycobacterium tuberculosis in superficially normal lung tissue during latent infection. Lancet 356(9248):2133–2138PubMedCrossRef

59.

Barrios-Payan J, Saqui-Salces M, Jeyanathan M, Alcantara-Vazquez A, Castanon-Arreola M, Rook G, Hernandez-Pando R (2012) Extrapulmonary locations of Mycobacterium tuberculosis DNA during latent infection. J Infect Dis 206(8):1194–1205PubMedCrossRef

60.

Clay H, Volkman HE, Ramakrishnan L (2008) Tumor necrosis factor signaling mediates resistance to mycobacteria by inhibiting bacterial growth and macrophage death. Immunity 29(2):283–294PubMedCrossRef

61.

Lin PL, Myers A, Smith L et al (2010) Tumor necrosis factor neutralization results in disseminated disease in acute and latent Mycobacterium tuberculosis infection with normal granuloma structure in a cynomolgus macaque model. Arthritis Rheum 62(2):340–350PubMed

62.

Iliopoulos A, Psathakis K, Aslanidis S, Skagias L, Sfikakis PP (2006) Tuberculosis and granuloma formation in patients receiving anti-TNF therapy. Int J Tuberc Lung Dis 10(5):588–590PubMed

63.

Bru A, Cardona P-J (2010) Mathematical modeling of tuberculosis bacillary counts and cellular populations in the organs of infected mice. PLoS ONE 5(9):e12985PubMedCrossRef

64.

Cardona P-J, Ivanyi J (2011) The secret trumps, impelling the pathogenicity of tubercle bacilli. Enferm Infecc Microbiol Clin 29(Suppl 1):14–19PubMedCrossRef

65.

Ramakrishnan L (2012) Revisiting the role of the granuloma in tuberculosis. Nat Rev Immunol 12(5):352–366PubMed

66.

Volkman HE, Pozos TC, Zheng J, Davis JM, Rawls JF, Ramakrishnan L (2010) Tuberculous granuloma induction via interaction of a bacterial secreted protein with host epithelium. Science 327(5964):466–469PubMedCrossRef

67.

Black GF, Thiel BA, Ota MO et al (2009) Immunogenicity of novel DosR regulon-encoded candidate antigens of Mycobacterium tuberculosis in three high-burden populations in Africa. Clin Vaccine Immunol 16(8):1203–1212PubMedCrossRef

68.

Schnappinger D, Schoolnik GK, Ehrt S (2006) Expression profiling of host pathogen interactions: how Mycobacterium tuberculosis and the macrophage adapt to one another. Microb Infect 8(4):1132–1140CrossRef

69.

Garton NJ, Waddell SJ, Sherratt AL et al (2008) Cytological and transcript analyses reveal fat and lazy persister-like bacilli in tuberculous sputum. PLoS Med 5(4):e75PubMedCrossRef

70.

Chegou NN, Black GF, Loxton AG et al (2012) Potential of novel Mycobacterium tuberculosis infection phase-dependent antigens in the diagnosis of TB disease in a high burden setting. BMC Infect Dis 12(1):10PubMedCrossRef

71.

Chegou NN, Essone PN, Loxton AG et al (2012) Potential of host markers produced by infection phase-dependent antigen-stimulated cells for the diagnosis of tuberculosis in a highly endemic area. PLoS ONE 7(6):e38501PubMedCrossRef

72.

Boon C, Dick T (2010) How Mycobacterium tuberculosis goes to sleep: the dormancy survival regulator DosR a decade later. Futur Microbiol 7(4):513–518CrossRef

73.

Wayne LG, Sohaskey CD (2001) Nonreplicating persistence of Mycobacterium tuberculosis. Annu Rev Microbiol 55:139–163PubMedCrossRef

74.

Keren I, Minami S, Rubin E, Lewis K (2011) Characterization and transcriptome analysis of Mycobacterium tuberculosis persisters. mBio 2(3):e00100–e00111PubMedCrossRef

75.

Manganelli R, Voskuil MI, Schoolnik GK, Smith I (2001) The Mycobacterium tuberculosis ECF sigma factor sigmaE: role in global gene expression and survival in macrophages. Mol Microbiol 41(2):423–437PubMedCrossRef

76.

Aagaard C, Hoang T, Dietrich J, Cardona P-J, Izzo A, Dolganov G, Schoolnik GK, Cassidy JP, Billeskov R, Andersen P (2011) A multistage tuberculosis vaccine that confers efficient protection before and after exposure. Nat Med 17(2):189–194PubMedCrossRef

77.

Mitchison D, Davies G (2012) The chemotherapy of tuberculosis: past, present and future [State of the art]. Int J Tuberc Lung Dis 16(6):724–732PubMedCrossRef

78.

Lienhardt C, Raviglione M, Spigelman M, Hafner R, Jaramillo E, Hoelscher M, Zumla A, Gheuens J (2012) New drugs for the treatment of tuberculosis: needs, challenges, promise, and prospects for the future. J Infect Dis 205(suppl 2):S241–S249PubMedCrossRef

79.

Gler MT, Skripconoka V, Sanchez-Garavito E et al (2012) Delamanid for multidrug-resistant pulmonary tuberculosis. N Engl J Med 366(23):2151–2160PubMedCrossRef

80.

Diacon AH, Donald PR, Pym A et al (2012) Randomized pilot trial of eight weeks of bedaquiline (TMC207) treatment for multidrug-resistant tuberculosis: long-term outcome, tolerability, and effect on emergence of drug resistance. Antimicrob Agents Chemother 56(6):3271–3276PubMedCrossRef

81.

Alffenaar JWC, van der Laan T, Simons S, van der Werf TS, van de Kasteele PJ, de Neeling H, van Soolingen D (2011) Susceptibility of clinical Mycobacterium tuberculosis isolates to a potentially less toxic derivate of linezolid, PNU-100480. Antimicrob Agents Chemother 55(3):1287–1289PubMedCrossRef

82.

Williams K, Minkowski A, Amoabeng O, Peloquin CA, Taylor D, Andries K, Wallis RS, Mdluli KE, Nuermberger EL (2012) Sterilizing activities of novel combinations lacking first- and second-line drugs in a murine model of tuberculosis. Antimicrob Agents Chemother 56(6):3114–3120PubMedCrossRef

83.

Pranger AD, Kosterink JGW, van Altena R, Aarnoutse RE, van der Werf TS, Uges DRA, Alffenaar J-WC (2011) Limited-sampling strategies for therapeutic drug monitoring of moxifloxacin in patients with tuberculosis. Ther Drug Monit 33(3):350–354PubMedCrossRef

84.

Pranger AD, van Altena R, Aarnoutse RE, van Soolingen D, Uges DRA, Kosterink JGW, van der Werf TS, Alffenaar JWC (2011) Evaluation of moxifloxacin for the treatment of tuberculosis: 3 years of experience. Eur Respir J 38(4):888–894PubMedCrossRef

85.

Alffenaar J-WC, van Altena R, Harmelink IM, Filguera P, Molenaar E, Wessels AMA, van Soolingen D, Kosterink JGW, Uges DRA, van der Werf TS (2010) Comparison of the pharmacokinetics of two dosage regimens of linezolid in multidrug-resistant and extensively drug-resistant tuberculosis patients. Clin Pharmacokinet 49(8):559–565PubMedCrossRef

86.

Alffenaar J-WC, Kosterink JGW, van Altena R, van der Werf TS, Uges DRA, Proost JH (2010) Limited sampling strategies for therapeutic drug monitoring of linezolid in patients with multidrug-resistant tuberculosis. Ther Drug Monit 32(1):97–101PubMedCrossRef

87.

Alffenaar JWC, van Altena R, Bökkerink HJ, Luijckx GJ, van Soolingen D, Aarnoutse RE, van der Werf TS (2009) Pharmacokinetics of moxifloxacin in cerebrospinal fluid and plasma in patients with tuberculous meningitis. Clin Infect Dis 49(7):1080–1082PubMedCrossRef

88.

Srivastava S, Pasipanodya JG, Gumbo T (2012) Reply to Alffenaar. J Infect Dis 205(11):1766CrossRef

89.

McShane H (2011) Tuberculosis vaccines: beyond bacille Calmette-Guerin. Philos Trans R Soc Lond B Biol Sci 366(1579):2782–2789PubMedCrossRef

90.

Kaufmann SH, Hussey G, Lambert P-H (2010) New vaccines for tuberculosis. Lancet 375(9731):2110–2119PubMedCrossRef

91.

Zwerling A, Behr MA, Verma A, Brewer TF, Menzies D, Pai M (2011) The BCG World Atlas: a database of global BCG vaccination policies and practices. PLoS Med 8(3):e1001012PubMedCrossRef

92.

Ottenhoff THM, Kaufmann SHE (2012) Vaccines against tuberculosis: where are we and where do we need to go? PLoS Pathog 8(5):e1002607–e1002612PubMedCrossRef

93.

Maleszewska M, Moonen J-RAJ, Huijkman N, van de Sluis B, Krenning G, Harmsen MC (2012) IL-1β and TGFβ2 synergistically induce endothelial to mesenchymal transition in an NFκB-dependent manner. Immunobiology. doi:10.1016/j.imbio.2012.05.026 PubMed

94.

Beresford B, Sadoff JC (2010) Update on research and development pipeline: tuberculosis vaccines. Clin Infect Dis 50(s3):S178–S183PubMedCrossRef

95.

Krenning G, Zeisberg EM, Kalluri R (2010) The origin of fibroblasts and mechanism of cardiac fibrosis. J Cell Physiol 225(3):631–637PubMedCrossRef

96.

Kaufmann SHE (2010) Future vaccination strategies against tuberculosis: thinking outside the box. Immunity 33(4):567–577PubMedCrossRef

97.

World Health Organization (2011) Global Plan to Stop TB. WHO, Geneva

98.

Skeiky YAW, Alderson MR, Ovendale PJ et al (2004) Differential immune responses and protective efficacy induced by components of a tuberculosis polyprotein vaccine, Mtb72F, delivered as naked DNA or recombinant protein. J Immunol 172(12):7618–7628PubMed

99.

Grange JM, Brunet LR, Rieder HL (2011) Immune protection against tuberculosis—when is immunotherapy preferable to vaccination? Tuberc (Edinb) 91(2):179–185CrossRef

100.

Suthar AB, Lawn SD, del Amo J et al (2012) Antiretroviral therapy for prevention of tuberculosis in adults with HIV: a systematic review and meta-analysis. PLoS Med 9(7):e1001270PubMedCrossRef

101.

von Reyn CF, Mtei L, Arbeit RD et al (2010) Prevention of tuberculosis in Bacille Calmette–Guérin-primed, HIV-infected adults boosted with an inactivated whole-cell mycobacterial vaccine. AIDS 24(5):675–685CrossRef

102.

Stanford JL, Grange JM (1994) The promise of immunotherapy for tuberculosis. Respir Med 88(1):3–7PubMedCrossRef

103.

Yang X-Y, Chen Q-F, Li Y-P, Wu S-M (2011) Mycobacterium vaccae as adjuvant therapy to anti-tuberculosis chemotherapy in never-treated tuberculosis patients: a meta-analysis. PLoS ONE 6(9):e23826PubMedCrossRef

104.

Vilaplana C, Montané E, Pinto S, Barriocanal AM, Domenech G, Torres F, Cardona PJ, Costa J (2010) Double-blind, randomized, placebo-controlled Phase I Clinical Trial of the therapeutical antituberculous vaccine RUTI^®. Vaccine 28(4):1106–1116PubMedCrossRef

105.

Hawkridge T, Mahomed H (2011) Prospects for a new, safer and more effective TB vaccine. Paediatr Respir Rev 12(1):46–51PubMedCrossRef

106.

Arjanova VO, Prihoda DN, Yurchenko VL, Sokolenko NI, Frolov MV (2010) Phase 2 trial of V-5 Immunitor (V5) in patients with chronic hepatitis C Co-infected with HIV and Mycobacterium tuberculosis. J Vaccines Vaccin 01(01):1–5CrossRef

107.

Butov DA, Pashkov YN, Stepanenko AL, Choporova AI, Butova TS, Batdelger D, Jirathitikal V, Bourinbaiar AS, Zaitzeva SI (2011) Phase IIb randomized trial of adjunct immunotherapy in patients with first-diagnosed tuberculosis, relapsed and multi-drug-resistant (MDR) TB. J Immune Based Ther Vaccines 9(1):3PubMedCrossRef

108.

Koch R (1891) A further communication on a remedy for tuberculosis. BMJ 1(1568):125–127PubMedCrossRef

109.

Gradmann C (2001) Robert Koch and the pressures of scientific research: tuberculosis and tuberculin. Med Hist 45(1):1–32PubMedCrossRef

110.

Die Atiologie der Tuberculose. Facsimile of the original contribution by Robert Koch in “Berliner Klinische Wochenschrift” 10 April 1882

111.

British Medical Research Council (1972) Controlled clinical trial of short-course (6-month) regimens of chemotherapy for treatment of pulmonary tuberculosis. Lancet 1(7760):1079–1085

112.

Grange JM (1997) Immunotherapy: a new strategy for tuberculosis control? Respir Med 91(1):1–4PubMedCrossRef

113.

Stanford J, Stanford C, Stansby G, Bottasso O, Bahr G, Grange J (2009) The common mycobacterial antigens and their importance in the treatment of disease. Curr Pharm Des 15(11):1248–1260PubMedCrossRef

114.

Camporota L, Corkhill A, Long H et al (2003) The effects of Mycobacterium vaccae on allergen-induced airway responses in atopic asthma. Eur Respir J 21(2):287–293PubMedCrossRef

115.

Fontanella GH, Pascutti MF, Daurelio L, Perez AR, Nocito AL, Wojdyla D, Bottasso O, Revelli SS, Stanford JL (2007) Improved outcome of Trypanosoma cruzi infection in rats following treatment in early life with suspensions of heat-killed environmental Actinomycetales. Vaccine 25(17):3492–3500PubMedCrossRef

116.

Stansby G, Chan YC, Berwanger CS, Shurey S, Rook GAW, Stanford JL (2002) Prevention of experimental myointimal hyperplasia by immunomodulation. Eur J Vasc Endovasc Surg 23(1):23–28PubMedCrossRef

117.

Abbot NC, Beck JS, Feval F, Weiss F, Mobayen MH, Ghazi Saidi K, Dowlati Y, Velayati AA, Stanford JL (2002) Immunotherapy with Mycobacterium vaccae and peripheral blood flow in long-treated leprosy patients, a randomised, placebo-controlled trial. Eur J Vasc Endovasc Surg 24(3):202–208PubMedCrossRef

118.

Stanford JL, Stanford CA, O’Brien MER, Grange JM (2008) Successful immunotherapy with Mycobacterium vaccae in the treatment of adenocarcinoma of the lung. Eur J Cancer 44(2):224–227PubMedCrossRef

119.

Marro A, Pirles M, Schiaffino L, Bin L, Dávila H, Bottasso OA, McIntyre G, Ripley PR, Stanford CA, Stanford JL (2011) Successful immunotherapy of canine flea allergy with injected Actinomycetales preparations. Immunotherapy 3(8):971–978PubMedCrossRef

120.

Ramu G, Prema GD, Balakrishnan S, Shanker Narayan NP, Stanford JL (1990) A preliminary report on the immunotherapy of psoriasis. Indian Med Gazette 124:381–382

121.

Lehrer A, Bressanelli A, Wachsmann V, Bottasso O, Bay ML, Singh M, Stanford C, Stanford J (1998) Immunotherapy with Mycobacterium vaccae in the treatment of psoriasis. FEMS Immunol Med Microbiol 21(1):71–77PubMedCrossRef

122.

Gil O, Guirado E, Gordillo S, Díaz J, Tapia G, Vilaplana C, Ariza A, Ausina V, Cardona P-J (2006) Intragranulomatous necrosis in lungs of mice infected by aerosol with Mycobacterium tuberculosis is related to bacterial load rather than to any one cytokine or T cell type. Microb Infect 8(3):628–636CrossRef

123.

Uhlin M, Andersson J, Zumla A, Maeurer M (2012) Adjunct immunotherapies for tuberculosis. J Infect Dis 205(suppl 2):S325–S334PubMedCrossRef

124.

Van Deun A, Maug AKJ, Hossain A, Gumusboga M, de Jong BC (2012) Fluorescein diacetate vital staining allows earlier diagnosis of rifampicin-resistant tuberculosis. Int J Tuberc Lung Dis 16(9):1174–1179PubMedCrossRef

125.

Hamid Salim A, Aung K, Hossain MA, Van Deun A (2006) Early and rapid microscopy-based diagnosis of true treatment failure and MDR-TB. Int J Tuberc Lung Dis 10(11):1248–1254PubMed

126.

Warmelink I, ten Hacken NH, van der Werf TS, van Altena R (2010) Weight loss during tuberculosis treatment is an important risk factor for drug-induced hepatotoxicity. Br J Nutr 105(03):400–408PubMedCrossRef

127.

Warmelink I, van Altena R, ten Hacken N, van der Werf T, van der Veer E (2011) Nutritional status and vitamin D3 during antimicrobial treatment. Lancet 377(9775):1407–1408PubMedCrossRef

128.

Campbell GR, Spector SA (2012) Vitamin D inhibits human immunodeficiency virus type 1 and Mycobacterium tuberculosis infection in macrophages through the induction of autophagy. PLoS Pathog 8(5):e1002689PubMedCrossRef

129.

Kempker RR, Vashakidze S, Solomonia N, Dzidzikashvili N, Blumberg HM (2012) Surgical treatment of drug-resistant tuberculosis. Lancet Infect Dis 12(2):157–166PubMedCrossRef

130.

Iddriss A, Padayatchi N, Reddy D, Reddi A (2012) Pulmonary resection for extensively drug resistant tuberculosis in Kwazulu-Natal, South Africa. Ann Thorac Surg 94(2):381–386

Title: Targeting multidrug-resistant tuberculosis (MDR-TB) by therapeutic vaccines
Authors: Satria A. Prabowo
Matthias I. Gröschel
Ed D. L. Schmidt
Alena Skrahina
Traian Mihaescu
Serap Hastürk
Rotislav Mitrofanov
Edita Pimkina
Ildikó Visontai
Bouke de Jong
John L. Stanford
Père-Joan Cardona
Stefan H. E. Kaufmann
Tjip S. van der Werf
Publication date: 01-04-2013
Publisher: Springer-Verlag
Published in: Medical Microbiology and Immunology / Issue 2/2013
Print ISSN: 0300-8584
Electronic ISSN: 1432-1831
DOI: https://doi.org/10.1007/s00430-012-0278-6

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Targeting multidrug-resistant tuberculosis (MDR-TB) by therapeutic vaccines

Abstract

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Abstract

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