Why don’t we have an effective tuberculosis vaccine yet?

References

• Organization WH. Global Tuberculosis report 2014. (2014).
   Google Scholar
• Trunz BB, Fine P, Dye C. Effect of BCG vaccination on childhood tuberculous meningitis and miliary tuberculosis worldwide: a meta-analysis and assessment of cost-effectiveness. Lancet. 2006;367(9517):1173–1180.
   PubMed Web of Science ®Google Scholar
• Fine PE. Variation in protection by BCG: implications of and for heterologous immunity. Lancet. 1995;346(8986):1339–1345.
   PubMed Web of Science ®Google Scholar
• Colditz GA, Berkey CS, Mosteller F, et al. The efficacy of bacillus Calmette-Guerin vaccination of newborns and infants in the prevention of tuberculosis: meta-analyses of the published literature. Pediatrics. 1995;96(1 Pt 1):29–35.
   PubMed Web of Science ®Google Scholar
• Rodrigues LC, Diwan VK, Wheeler JG. Protective effect of BCG against tuberculous meningitis and miliary tuberculosis: a meta-analysis. Int J Epidemiol. 1993;22(6):1154–1158.
   PubMed Web of Science ®Google Scholar
• Ganguly N, Siddiqui I, Sharma P. Role of M. tuberculosis RD-1 region encoded secretory proteins in protective response and virulence. Tuberculosis (Edinb). 2008;88(6):510–517.
   PubMed Web of Science ®Google Scholar
• Stanley SA, Raghavan S, Hwang WW, et al. Acute infection and macrophage subversion by Mycobacterium tuberculosis require a specialized secretion system. Proc Natl Acad Sci U S A. 2003;100(22):13001–13006.
   PubMed Web of Science ®Google Scholar
• Pathak SK, Basu S, Basu KK, et al. Direct extracellular interaction between the early secreted antigen ESAT-6 of Mycobacterium tuberculosis and TLR2 inhibits TLR signaling in macrophages. Nat Immunol. 2007;8(6):610–618.
   PubMed Web of Science ®Google Scholar
• Ganguly N, Giang PH, Gupta C, et al. Mycobacterium tuberculosis secretory proteins CFP-10, ESAT-6 and the CFP10: ESAT6 complex inhibit lipopolysaccharide-induced NF-[kappa]B transactivation by downregulation of reactive oxidative species (ROS) production. Immunol Cell Biol. 2007;86(1):98–106.
   PubMed Web of Science ®Google Scholar
• de Jonge MI, Pehau-Arnaudet G, Fretz MM, et al. ESAT-6 from Mycobacterium tuberculosis dissociates from its putative chaperone CFP-10 under acidic conditions and exhibits membrane-lysing activity. J Bacteriol. 2007;189(16):6028–6034.
   PubMed Web of Science ®Google Scholar
• Ritz N, Hanekom WA, Robins-Browne R, et al. Influence of BCG vaccine strain on the immune response and protection against tuberculosis. FEMS Microbiol Rev. 2008;32(5):821–841.
   PubMed Web of Science ®Google Scholar
• Behr MA, Small PM. A historical and molecular phylogeny of BCG strains. Vaccine. 1999;17(7–8):915–922.
   PubMed Web of Science ®Google Scholar
• Lagranderie MR, Balazuc AM, Deriaud E, et al. Comparison of immune responses of mice immunized with five different Mycobacterium bovis BCG vaccine strains. Infect Immun. 1996;64(1):1–9.
   PubMed Web of Science ®Google Scholar
• Mangtani P, Abubakar I, Ariti C, et al. Protection by BCG vaccine against tuberculosis: a systematic review of randomized controlled trials. Clin Infect Dis. 2014;58(4):470–480.
   PubMed Web of Science ®Google Scholar
• Venkataswamy MM, Goldberg MF, Baena A, et al. In vitro culture medium influences the vaccine efficacy of Mycobacterium bovis BCG. Vaccine. 2012;30(6):1038–1049.
   PubMed Web of Science ®Google Scholar
• Black GF, Weir RE, Floyd S, et al. BCG-induced increase in interferon-gamma response to mycobacterial antigens and efficacy of BCG vaccination in Malawi and the UK: two randomised controlled studies. Lancet. 2002;359(9315):1393–1401.
   PubMed Web of Science ®Google Scholar
• Brandt L, Feino Cunha J, Weinreich Olsen A, et al. Failure of the Mycobacterium bovis BCG vaccine: some species of environmental mycobacteria block multiplication of BCG and induction of protective immunity to tuberculosis. Infect Immun. 2002;70(2):672–678.
   PubMed Web of Science ®Google Scholar
• Brennan MJ, Thole J. Tuberculosis vaccines: a strategic blueprint for the next decade. Tuberculosis (Edinb). 2012;92(Suppl 1):S6–13.
   PubMed Web of Science ®Google Scholar
• Tameris MD, Hatherill M, Landry BS, et al. Safety and efficacy of MVA85A, a new tuberculosis vaccine, in infants previously vaccinated with BCG: a randomised, placebo-controlled phase 2b trial. Lancet. 2013;381(9871):1021–1028.
   PubMed Web of Science ®Google Scholar
• Manjaly Thomas Z-R, McShane H. Aerosol immunisation for TB: matching route of vaccination to route of infection. Trans R Soc Trop Med Hyg. 2015;109(3):175–181.
   PubMed Web of Science ®Google Scholar
• Sharpe S, White A, Gleeson F, et al. Ultralow dose aerosol challenge with Mycobacterium tuberculosis leads to divergent outcomes in rhesus and cynomolgus macaques. Tuberculosis. 2016;96:1–12.
   PubMed Web of Science ®Google Scholar
• Frieden TR, Sterling TR, Munsiff SS, et al. Tuberculosis. Lancet. 2003;362(9387):887–899.
   PubMed Web of Science ®Google Scholar
• Wolf AJ, Linas B, Trevejo-Nunez GJ, et al. Mycobacterium tuberculosis infects dendritic cells with high frequency and impairs their function in vivo. J Immunol. 2007;179(4):2509–2519.
   PubMed Web of Science ®Google Scholar
• Mortaz E, Adcock IM, Tabarsi P, et al. Interaction of pattern recognition receptors with Mycobacterium Tuberculosis. J Clin Immunol. 2015 Jan;35(1):1–10. doi: 10.1007/s10875-014-0103-7. [Epub 2014 Oct 14].
   Google Scholar
• Dannenberg AM Jr. Roles of cytotoxic delayed-type hypersensitivity and macrophage-activating cell-mediated immunity in the pathogenesis of tuberculosis. Immunobiology. 1994;191(4–5):461–473.
   PubMed Web of Science ®Google Scholar
• Dannenberg AM Jr. Pathogenesis of pulmonary Mycobacterium bovis infection: basic principles established by the rabbit model. Tuberculosis (Edinb). 2001;81(1–2):87–96.
   PubMed Web of Science ®Google Scholar
• Lawn SD, Zumla AI. Tuberculosis. Lancet. 2011;378(9785):57–72.
   PubMed Web of Science ®Google Scholar
• Cambier CJ, Takaki KK, Larson RP, et al. Mycobacteria manipulate macrophage recruitment through coordinated use of membrane lipids. Nature. 2014;505(7482):218–222.
   PubMed Web of Science ®Google Scholar
• Puri RV, Reddy PV, Tyagi AK. Secreted acid phosphatase (SapM) of Mycobacterium tuberculosis is indispensable for arresting phagosomal maturation and growth of the pathogen in guinea pig tissues. PLoS One. 2013;8(7):e70514.
   PubMed Web of Science ®Google Scholar
• Bach H, Papavinasasundaram KG, Wong D, et al. Mycobacterium tuberculosis virulence is mediated by PtpA dephosphorylation of human vacuolar protein sorting 33B. Cell Host Microbe. 2008;3(5):316–322.
   PubMed Web of Science ®Google Scholar
• Wang J, Li B-X, Ge P-P, et al. Mycobacterium tuberculosis suppresses innate immunity by coopting the host ubiquitin system. Nat Immunol. 2015;16(3):237–245.
   PubMed Web of Science ®Google Scholar
• Mehra A, Zahra A, Thompson V, et al. Mycobacterium tuberculosis type VII secreted effector EsxH targets host ESCRT to impair trafficking. PLoS Pathog. 2013;9(10):e1003734.
   PubMed Web of Science ®Google Scholar
• Shukla S, Richardson ET, Athman JJ, et al. Mycobacterium tuberculosis lipoprotein LprG binds lipoarabinomannan and determines its cell envelope localization to control phagolysosomal fusion. PLoS Pathog. 2014;10(10):e1004471.
   Google Scholar
• Gaur RL, Ren K, Blumenthal A, et al. LprG-mediated surface expression of lipoarabinomannan is essential for virulence of Mycobacterium tuberculosis. PLoS Pathog. 2014;10(9):e1004376.
   PubMed Web of Science ®Google Scholar
• Guenin-Mace L, Simeone R, Demangel C. Lipids of pathogenic Mycobacteria: contributions to virulence and host immune suppression. Transbound Emerg Dis. 2009;56(6–7):255–268.
   PubMed Web of Science ®Google Scholar
• Sun J, Singh V, Lau A, et al. Mycobacterium tuberculosis nucleoside diphosphate kinase inactivates small GTPases leading to evasion of innate immunity. PLoS Pathog. 2013;9(7):e1003499.
   PubMed Web of Science ®Google Scholar
• Deffert C, Cachat J, Krause K-H. Phagocyte NADPH oxidase, chronic granulomatous disease and mycobacterial infections. Cell Microbiol. 2014;16(8):1168–1178.
   PubMed Web of Science ®Google Scholar
• Kumar A, Farhana A, Guidry L, et al. Redox homeostasis in mycobacteria: the key to tuberculosis control? Expert Rev Mol Med. 2011;13:e39.
   PubMed Web of Science ®Google Scholar
• Szulc-Kielbik I, Brzezinska M, Kielbik M, et al. Mycobacterium tuberculosis RecA is indispensable for inhibition of the mitogen-activated protein kinase-dependent bactericidal activity of THP-1-derived macrophages in vitro. FEBS J. 2015 Apr;282(7):1289–1306. doi: 10.1111/febs.13219. [Epub 2015 Feb 13].
   PubMed Web of Science ®Google Scholar
• Kalia D, Merey G, Nakayama S, et al. Nucleotide, c-di-GMP, c-di-AMP, cGMP, cAMP, (p)ppGpp signaling in bacteria and implications in pathogenesis. Chem Soc Rev. 2013;42(1):305–341.
   PubMed Web of Science ®Google Scholar
• Kalamidas SA, Kuehnel MP, Peyron P, et al. cAMP synthesis and degradation by phagosomes regulate actin assembly and fusion events: consequences for mycobacteria. J Cell Sci. 2006;119(Pt 17):3686–3694.
   PubMed Web of Science ®Google Scholar
• Shenoy AR, Visweswariah SS. New messages from old messengers: cAMP and mycobacteria. Trends Microbiol. 2006;14(12):543–550.
   PubMed Web of Science ®Google Scholar
• Schmelzle T, Beck T, Martin DE, et al. Activation of the RAS/cyclic AMP pathway suppresses a TOR deficiency in yeast. Mol Cell Biol. 2004;24(1):338–351.
   PubMed Web of Science ®Google Scholar
• Deretic V, Saitoh T, Akira S. Autophagy in infection, inflammation and immunity. Nat Rev Immunol. 2013;13(10):722–737.
   PubMed Web of Science ®Google Scholar
• Deretic V, Kimura T, Timmins G, et al. Immunologic manifestations of autophagy. J Clin Invest. 2015;125(1):75–84.
   PubMed Web of Science ®Google Scholar
• Cooper AM. Cell-mediated immune responses in tuberculosis. Annu Rev Immunol. 2009;27:393–422.
   PubMed Web of Science ®Google Scholar
• Orme IM, Basaraba RJ. The formation of the granuloma in tuberculosis infection. Semin Immunol. 2014;26(6):601–609.
   PubMed Web of Science ®Google Scholar
• Flynn JL, Chan J, Triebold KJ, et al. An essential role for interferon gamma in resistance to Mycobacterium tuberculosis infection. J Exp Med. 1993;178(6):2249–2254.
   PubMed Web of Science ®Google Scholar
• Cooper AM, Dalton DK, Stewart TA, et al. Disseminated tuberculosis in interferon gamma gene-disrupted mice. J Exp Med. 1993;178(6):2243–2247.
   PubMed Web of Science ®Google Scholar
• Editorial. Canadian Experience with BCG Vaccine. Can Med Assoc J. 1936;35(2):196–197.
   PubMedGoogle Scholar
• Aronson JD. Protective vaccination against tuberculosis, with special reference to BCG vaccine. Minn Med. 1948;31(12):1336.
   PubMedGoogle Scholar
• Levine MI, Sackett MF. Results of BCG immunization in New York City. Am Rev Tuberc. 1946;53:517–532.
   PubMedGoogle Scholar
• Tribouley J, Tribouley-Duret J, Appriou M. [Effect of Bacillus Callmette Guerin (BCG) on the receptivity of nude mice to Schistosoma mansoni]. C R Seances Soc Biol Fil. 1978;172(5):902–904.
   PubMedGoogle Scholar
• Van ‘t Wout JW, Poell R, Van Furth R. The role of BCG/PPD-activated macrophages in resistance against systemic candidiasis in mice. Scand J Immunol. 1992;36(5):713–719.
   PubMed Web of Science ®Google Scholar
• Saeed S, Quintin J, Kerstens HH, et al. Epigenetic programming of monocyte-to-macrophage differentiation and trained innate immunity. Science. 2014;345(6204):1251086.
   PubMed Web of Science ®Google Scholar
• Kenneth Murphy PT, Walport M. Janeway’s immunobiology. In Murphy, Travers and Walport. 7th ed. 2007. New York, NY: Garland Science.
   Google Scholar