REVIEW PAPER
Vaccine research and development: tuberculosis as a global health threat
More details
Hide details
Submission date: 2015-11-12
Final revision date: 2016-11-10
Acceptance date: 2017-01-10
Publication date: 2017-08-08
Cent Eur J Immunol 2017;42(2):196-204
KEYWORDS
ABSTRACT
One of the aims of the World Health Organisation (WHO) Millennium Development Goals (MDG) is to reduce the number of cases of tuberculosis (TB) infection by the year 2015. However, 9 million new cases were reported in 2013, with an estimated 480,000 new cases of multi-drug resistant tuberculosis (MDR-TB) globally. Bacille Calmette-Guérin (BCG) is the most available and currently used candidate vaccine against tuberculosis; it prevents childhood TB, but its effectiveness against pulmonary TB in adults and adolescents is disputed. To achieve the goal of the WHO MDG, the need for a new improved vaccine is of primary importance. This review highlights several articles that have reported vaccine development. There are about 16 TB vaccines in different phases of clinical trials at the time of writing, which include recombinant peptide/protein, live-attenuated and recombinant live-attenuated, protein/adjuvant, viral-vectored, and immunotherapeutic vaccine. Further studies in reverse vaccinology and massive campaigns on vaccination are needed in order to achieve the target for TB eradication by 2050.
REFERENCES (109)
1.
Yuen CM, Weyenga HO, Kim AA, et al. (2014): Comparison of trends in tuberculosis incidence among adults living with HIV and adults without HIV – Kenya, 1998-2012. Plos One 9: e99880.
2.
WHO, Global Tubeculosis Report (2012): WHO, Geneva, Switzerland. 2012, WHO/HTM/TB/2012.6.
3.
Theron G, Zijenah L, Chanda D, et al. (2014): Feasibility, accuracy, and clinical effect of point-of-care Xpert MTB/RIF testing for tuberculosis in primary-care settings in Africa: a multicentre, randomised, controlled trial. Lancet 383: 424-435.
4.
Finnie RK, Khoza LB, van den Borne B, et al. (2011): Factors associated with patient and health care system delay in diagnosis and treatment for TB in Sub-saharan African countries with high burdens of TB and HIV. Trop Med Int Health 16: 394-411.
5.
Harries AD, Zachariah R, Corbett EL, et al. (2010): The HIV-associated tuberculosis epidemic – when will we act? Lancet 375: 1906-1919.
6.
Müller B, Borrell S, Rose G, Gagneux S (2013): The heterogeneous evolution of multidrug-resistant Mycobacterium tuberculosis. Trends Genet 29: 160-169.
7.
Russell DG, Barry CE, Flynn JL (2010): Tuberculosis: what we don’t know can, and does, hurt us. Science 328: 852-856.
8.
Hartman-Adams H, Clark K, Juckett G (2014): Update on latent tuberculosis infection. Am Fam Physician 89: 889-896.
9.
Vandemoortele J (2004): Are the millennium development goals feasible? In: Targeting development: critical perspectives on the millennium development goals. Richard B, Howard W (eds.). Taylor & Francis Group 124-144.
10.
Devarajan S, Miller M, Swanson EV (2002): Goals for development: History, prospects, and costs. World Bank Policy Research Working Paper (2819).
11.
WHO, Global Tubeculosis Report (2015): WHO, Geneva Switzerland. 2015. WHO/HTM/TB/2015.22.
12.
Copin R, Coscollá M, Efstathiadis E, et al. (2014): Impact of in vitro evolution on antigenic diversity of Mycobacterium bovis bacillus Calmette-Guerin (BCG). Vaccine 32: 5998-6004.
13.
Kaufmann SH (2014): Tuberculosis vaccine development at a divide. Curr Opin Pulm Med 20: 294-300.
14.
Kaufmann SH, Hussey G, Lambert PH (2010): New vaccines for tuberculosis. Lancet 375: 2110-2119.
15.
Galagan JE (2014): Genomic insights into tuberculosis. Nat Rev Genet 15: 307-320.
16.
Girard MP, Fruth U, Kieny MP (2005): A review of vaccine research and development: tuberculosis. Vaccine 23: 5725-5731.
17.
Kakchapati S, Choonpradub C, Lim A (2014): Spatial and temporal variations in tuberculosis incidence, Nepal. Southeast Asian J Trop Med Public Health 45: 95-102.
18.
WHO, Global Tuberculosis Report (2014): WHO, Geneva, Switzerland. 2014. WHO/HTM/TB/2014.08.
19.
Modjarrad K, Vermund SH (2010): Effect of treating co-infections on HIV-1 viral load: a systematic review: Lancet Infect Dis 10: 455-463.
20.
Ahmed A, Rakshit S, Vyakarnam A (2016): HIV-TB co-infection: mechanisms that drive reactivation of Mycobacterium tuberculosis in HIV infection. Oral Dis 22 (S1): 53-60.
21.
WHO, Global Tuberculosis Report (2013): WHO, Geneva, Switzerland. 2013. WHO/HTM/TB/2013.11.
22.
Stuckler D, Basu S, McKee M, Lurie M (2011): Mining and risk of tuberculosis in Sub-saharan Africa. Am J Public Health 101: 524-530.
23.
Rosilawati ML, Yasmon A (2012): Detection of multidrug-resistant Mycobacterium tuberculosis directly from sputum samples of patients from Jakarta, Indonesia by radioisotope-based PCR-dot blot hybridization. Southeast Asian J Trop Med Public Health 43: 89-95.
24.
Abubakar I, Zignol M, Falzon D, et al. (2013): Drug-resistant tuberculosis: time for visionary political leadership. Lancet Infect Dis 13: 529-539.
25.
Udwadia ZF, Amale RA, Ajbani KK, Rodrigues C (2012): Totally drug-resistant tuberculosis in India. Clin Infect Dis 54: 579-581.
26.
Luca S, Mihaescu T (2013): History of BCG vaccine. Maedica (Buchar) 8: 53-58.
27.
Ryan K, Ray C (eds.) (2004): Sherris Medical Microbiology. 4th ed. 2004, McGraw Hill.
28.
Randall PJ, Hsu N, Quesniaux V, et al. (2015): Mycobacterium tuberculosis infection of the ‘non-classical immune cell’. Immunol Cell Biol 93: 789-795.
29.
Forrellad MA, Klepp LI, Gioffré A, et al. (2013): Virulence factors of the Mycobacterium tuberculosis complex. Virulence 4: 3-66.
30.
Fukuda T, Matsumura T, Ato M, et al. (2013): Critical roles for lipomannan and lipoarabinomannan in cell wall integrity of mycobacteria and pathogenesis of tuberculosis. MBio 4: e00472-12.
31.
Jones-López EC, Namugga O, Mumbowa F, et al. (2013): Cough aerosols of Mycobacterium tuberculosis Predict New Infection. A Household Contact Study. Am J Respir Crit Care Med 187: 1007-1015.
32.
Monin L, Khader SA (2014): Chemokines in tuberculosis: The good, the bad and the ugly. Semin Immunol 26: 552-558.
33.
Matucci A, Maggi E, Vultaggio A (2014): Cellular and humoral immune responses during tuberculosis infection: useful knowledge in the era of biological agents. J Rheumatol 91: 17-23.
34.
Saraav I, Singh S, Sharma S (2014): Outcome of Mycobacterium tuberculosis and Toll-like receptor interaction: immune response or immune evasion? Immunol Cell Biol 92: 741-746.
35.
Behar SM, Martin CJ Booty MG, et al. (2011): Apoptosis is an innate defense function of macrophages against Mycobacterium tuberculosis. Mucosal Immunol 4: 279-287.
36.
Ahmad S (2010): Pathogenesis, immunology, and diagnosis of latent Mycobacterium tuberculosis infection. Clin Dev Immunol 2011: 814943.
37.
Kozakiewicz L, Phuah J, Flynn J, Chan J (2013): The role of B cells and humoral immunity in Mycobacterium tuberculosis Infection. In: The new paradigm of immunity to tuberculosis. Adv Exp Med Biol 783: 225-250.
38.
Madan-Lala R, Sia JK, King R, et al. (2014): Mycobacterium tuberculosis impairs dendritic cell functions through the serine hydrolase Hip1. J Immunol 192: 4263-4272.
39.
Lambrecht BN, Nety K, GeurtsvanKessel CH, Hammad H (2013): Lung dendritic cells and pulmonary defence mechanisms to bacteria. In: Mucosal immunology of acute bacterial pneumonia. Prince A (ed). 2013; 49-66.
40.
Morris D, Gonzalez B, Khurasany M, et al. (2013): Characterization of dendritic cell and regulatory T cell functions against Mycobacterium tuberculosis infection. Biomed Res Int 2013: 402827.
41.
Kaufmann SH (2013): Tuberculosis vaccines: time to think about the next generation. Semin Immunol 25: 172-181.
42.
Mustafa AS, Al-Saidi F, El-Shamy AM, Al-Attiyh R (2011): Cytokines in response to proteins predicted in genomic regions of difference of Mycobacterium tuberculosis. Microbiol Immunol 55: 267-278.
43.
Gopal R, Monin L, Slight S, et al. (2014): Unexpected role for IL-17 in protective immunity against hypervirulent Mycobacterium tuberculosis HN878 infection. Plos Pathog 10: e1004099.
44.
Andersen P, Woodworth JS (2014): Tuberculosis vaccines–rethinking the current paradigm. Trends Immunol 35: 387-395.
45.
Duque-Correa MA, Kühl AA, Rodriguez PC, et al. (2014): Macrophage arginase-1 controls bacterial growth and pathology in hypoxic tuberculosis granulomas. Proc Natl Acad Sci 111: E4024-E4032.
46.
Ottenhoff T, Kaufmann S (2012): Vaccines against tuberculosis: where are we and where do we need to go. PLoS Pathog 8: e1002607.
47.
Andersen P, Kaufmann SH (2014): Novel vaccination strategies against tuberculosis. Cold Spring Harb Perspect Med 4: a018523.
48.
Nikolova M, Markova R, Drenska R, et al. (2013): Antigen-specific CD4-and CD8-positive signatures in different phases of Mycobacterium tuberculosis infection. Diagn Microbiol Infect Dis 75: 277-281.
49.
Green AM, DiFazio R, Flynn JL (2013): IFN- from CD4 T cells is essential for host survival and enhances CD8.
50.
T cell function during Mycobacterium tuberculosis infection. J Immunol 190: 270-277.
51.
Desvignes L, Wolf AJ, Ernst JD (2012): Dynamic roles of type I and type II IFNs in early infection with Mycobacterium tuberculosis. J Immunol 188: 6205-6215.
52.
Sharma S, Kalia NP, Suden P, et al. (2014): Protective efficacy of piperine against Mycobacterium tuberculosis. Tuberculosis 94: 389-396.
53.
Wareham AS, Tree JA, Marsh PD, et al. (2014): Evidence for a role for interleukin-17, Th17 cells and iron homeostasis in protective immunity against tuberculosis in cynomolgus macaques. PloS One 9: e88149.
54.
Rivas-Santiago B, Castańeda-Delgado JE, Santiago CER, et al. (2013): Ability of innate defence regulator peptides IDR-1002, IDR-HH2 and IDR-1018 to protect against Mycobacterium tuberculosis infections in animal models. PloS One 8: e59119.
55.
Rivas-Santiago B, Serrano CJ, Enciso-Moreno JA (2009): Susceptibility to infectious diseases based on antimicrobial peptide production. Infect Immun 77: 4690-4695.
56.
Gopal R, Khader SA (2013): Vaccines against tuberculosis: moving forward with new concepts. Expert Rev Vaccines 12: 829-831.
57.
Schito M, Migliori GB, Fletcher HA, et al. (2015): Perspectives on advances in tuberculosis diagnostics, drugs, and vaccines. Clin Infect Dis 61 (suppl 3): S102-S118.
58.
Whole mycobacteria cell vaccines for tuberculosis summary group (2015): Developing whole mycobacteria cell vaccines for tuberculosis: Workshop proceedings, Max Planck Institute for Infection Biology, Berlin, Germany, July 9, 2014. Vaccine 33: 3047-3055.
59.
Montagnani C, Chiappini E, Galli, L, de Martino M (2014): Vaccine against tuberculosis: what’s new? BMC Infect Dis 14 (Suppl 1): S2.
60.
Hawkridge T, Mahomed H (2011): Prospects for a new, safer and more effective TB vaccine. Paediatr Respir Rev 12: 46-51.
61.
Ocampo M (2015): Vaccines-Recent advances and clinical trials. In: Tuberculosis-expanding knowledge. Wellman R (eds.). InTech 103-121.
62.
Frick M (2015): The tuberculosis vaccines pipeline: A new path to the same destination? In: Pipeline report HIV, hepatitis C virus and tuberculosis drugs, diagnostics, vaccines, preventive technologies towards a cure and immune-based and gene therapies in development. Anderea B (eds.). HIV i-Base/Treatment action group. 163-178.
63.
Ahsan MJ (2015): Recent advances in the development of vaccines for tuberculosis. Ther Adv Vaccines 3: 66-75.
64.
Jefferys R (2012): The tuberculosis vaccine pipeline. HIV treatment bulletin. HIV i-Base. 251.
65.
Kaufmann SHE, Hussey G, Lambert PH (2010): New vaccines for tuberculosis. Lancet 375: 2110-2119.
66.
da Costa C, Walker B, Bonavia A (2015): Tuberculosis Vaccines – state of the art, and novel approaches to vaccine development. Intl J Infect Dis 32: 5-12.
67.
Wingfield C and Jefferys R (2011): The Tuberculosis vaccine pipeline. In: Pipeline report HIV, hepatitis C virus and tuberculosis drugs, diagnostics, vaccines, preventive technologies. 2nd edition. HIV i-Base/Treatment action group. 155-162.
68.
da Costa AC, Nogueira SV, Kipnis A, Junqueira-Kipnis, AP: Recombinant BCG: innovations on an old vaccine. Scope of BCG strains and strategies to improve long-lasting memory. In: Significance of antegen and epitope specificity in tuberculosis. Juray I, Tom HMO (eds.). Front Immunol 2014; 5.
69.
Norouzi S, Aghamohammadi A, Mamishi S, et al. (2012): Bacillus Calmette-Guérin (BCG) complications associated with primary immunodeficiency diseases. J Infect 64: 543-554.
70.
Poyntz HC, Stylianou E, Griffiths KL, et al. (2014): Non-tuberculous mycobacteria have diverse effects on BCG efficacy against Mycobacterium tuberculosis. Tuberculosis 94: 226-237.
71.
Mirlekar B, Pathak S, Pathade G (2012): Mycobacterium tuberculosis: approach to development of improved strategies for disease control through vaccination and immunodiagnosis. Indian J Lepr 85: 65-78.
72.
Deng Y, Bao L, Yang X (2011): Evaluation of immunogenicity and protective efficacy against Mycobacterium tuberculosis infection elicited by recombinant Mycobacterium bovis BCG expressing human Interleukin-12p70 and Early Secretory Antigen Target-6 fusion protein. Microbiol Immunol 55: 798-808.
73.
Fine PE (1995): Variation in protection by BCG: implications of and for heterologous immunity. Lancet 346: 1339-1345.
74.
Yuan W, Dong N, Zhang L, et al. (2012): Immunogenicity and protective efficacy of a tuberculosis DNA vaccine expressing a fusion protein of Ag85B-Esat6-HspX in mice. Vaccine 30: 2490-2497.
75.
Samuchiwal SK, Tousif S, Singh DK, et al. (2014): A peptide fragment from the human COX3 protein disrupts association of Mycobacterium tuberculosis virulence proteins ESAT-6 and CFP10, inhibits mycobacterial growth and mounts protective immune response. BMC Infect Dis 14: 355.
76.
Marchant A, Goetghebuer T, Ota MO, et al. (1999): Newborns develop a Th1-type immune response to Mycobacterium bovis bacillus Calmette-Guerin vaccination. J Immunol 163: 2249-2255.
77.
Mangtani P, Abubakar I, Ariti C, et al. (2014): Protection by BCG vaccine against tuberculosis: a systematic review of randomized controlled trials. Clin Infect Dis 58: 470-480.
78.
Barreto ML, Pereira SM, Ferreira AA (2006): BCG vaccine: efficacy and indications for vaccination and revaccination.
79.
J Pediatr (Rio J) 82: s45-s54.
80.
Principi N, Esposito S (2015): The present and future of tuberculosis vaccinations. Tuberculosis 95: 6-13.
81.
Moliva JI, Turner J, Torrelles JB (2015): Prospects in Mycobacterium bovis Bacille Calmette et Guérin (BCG) vaccine diversity and delivery: Why does BCG fail to protect against tuberculosis? Vaccine 33: 5035-5041.
82.
Nguipdop-Djomo P, Heldal E, Rodrigues LC, et al. (2016): Duration of BCG protection against tuberculosis and change in effectiveness with time since vaccination in Norway: a retrospective population-based cohort study. Lancet Infect Dis 16: 219-226.
83.
Bruffaerts N, Romano M, Denis O, et al. (2014): Increasing the vaccine potential of live M. bovis BCG by coadministration with plasmid DNA encoding a tuberculosis prototype antigen. Vaccines 2: 181-195.
84.
Bernatowska E, Wolska-Kuśnierz B, Pac M, et al. (2007): Clinical guidelines Risk of BCG infection in primary immunodeficiency children. Proposal of diagnostic, prophylactic and therapeutic guidelines for disseminated BCG based on experience in the Department of Immunology, Children’s Memorial Health Institute in Warsaw between 1980-2006. Kardiol Pol 65: 1307-1311.
85.
Pac M, Bustamante J, Buda P, et al. (2012): Disseminated Mycobacterium tuberculosis complex infection in a girl with partial dominant IFN- receptor 1 deficiency. Centr Eur Immunol 37: 378-381.
86.
Sarhan MA (2010): Tuberculosis vaccine. Saudi Med J 31: 9-13.
87.
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.
88.
Horwitz MA, Harth G, Dillon BJ, Masleša-Galić S (2000): Recombinant bacillus Calmette–Guérin (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 97: 13853-13858.
89.
Horwitz MA, Harth G (2003): A new vaccine against tuberculosis affords greater survival after challenge than the current vaccine in the guinea pig model of pulmonary tuberculosis. Infect Immun 71: 1672-1679.
90.
Hoft DF, Blazevic A, Abate G, et al. (2008): A new recombinant bacille Calmette-Guerin vaccine safely induces significantly enhanced tuberculosis-specific immunity in human volunteers. J Infect Dis 198: 1491-1501.
91.
Orme IM (2013): Vaccine development for tuberculosis: current progress. Drugs 73: 1015-1024.
92.
Svenson S, Källenius G, Pawlowski A, Hamasur B (2010): Towards new tuberculosis vaccine. Hum Vaccin 6: 309-317.
93.
Bottai D, Frigui W, Clark S, et al. (2015): Increased protective efficacy of recombinant BCG strains expressing virulence-neutral proteins of the ESX-1 secretion system. Vaccine 33: 2710-2718.
94.
Wang C, Fu R, Chen Z, et al. (2012): Immunogenicity and protective efficacy of a novel recombinant BCG strain overexpressing antigens Ag85A and Ag85B. Clin Dev Immunol 568383.
95.
Unnikrishnan M, Rappuoli R, and Serruto D (2012): Recombinant bacterial vaccines. Curr Opin Immunol 24: 337-342.
96.
Yu D, Hu X, Cai X (2008): Efficient tuberculosis treatment in mice using chemotherapy and immunotherapy with the combined DNA vaccine encoding Ag85B, MPT-64 and MPT-83. Gene Ther 15: 652-659.
97.
Li W, Deng G, Li M, et al. (2014): A recombinant adenovirus expressing CFP10, ESAT6, Ag85A and Ag85B of Mycobacterium tuberculosis elicits strong antigen-specific immune responses in mice. Mol Immunol 62: 86-95.
98.
Reed SG, Bertholet S, Coler RN, Friede M (2009): New horizons in adjuvants for vaccine development. Trends Immunol 30: 23-32.
99.
Ottenhoff TH, Doherty TM, van Dissel JT, et al. (2010): First in humans: a new molecularly defined vaccine shows excellent safety and strong induction of long-lived Mycobacterium tuberculosis-specific Th1-cell like responses. Hum Vaccin 6: 1007-1015.
100.
Reither K, Katsoulis L, Beattie T, et al. (2014): Safety and immunogenicity of H1/IC31®, an adjuvanted TB subunit vaccine, in HIV-Infected adults with CD4+ Lymphocyte Counts Greater than 350 cells/mm3: A Phase II, multi-Centre, double-blind, randomized, placebo-controlled trial. PloS One 9: e114602.
101.
Billeskov R, Elvang TT, Andersen PL, Dietrich J (2012): The HyVac4 subunit vaccine efficiently boosts BCG-primed anti-mycobacterial protective immunity. PLoS One 7: e39909.
102.
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.
103.
Thacher EG, Cavassini M, Audran R, et al. (2014): Safety and immunogenicity of the M72/AS01 candidate tuberculosis vaccine in HIV-infected adults on combination antiretroviral therapy: a phase I/II, randomized trial. AIDS 28: 1769-1781.
104.
Ruiz Manzano J, Vilaplana C (2014): Will we be treating tuberculosis with vaccines in the XXI Century? Arch Bronconeumol (English Version) 50: 373-374.
105.
Cardona PJ (2006): RUTI: A new chance to shorten the treatment of latent tuberculosis infection. Tuberculosis 86: 273-289.
106.
Nell AS, D’lom E, Bouic P, et al. (2014): Safety, tolerability, and immunogenicity of the novel antituberculous vaccine RUTI: randomized, placebo-controlled phase II clinical trial in patients with latent tuberculosis infection. PloS One 9: e89612.
107.
McShane H (2011): Tuberculosis vaccines: beyond bacille Calmette–Guérin. Philosophical transactions of the royal society B: Biological Sciences 366: 2782-2789.
108.
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: 675-685.
109.
Churchyard GJ, Snowden MA, Hokey D, et al. (2015): The safety and immunogenicity of an adenovirus type 35-vectored TB vaccine in HIV-infected, BCG-vaccinated adults with CD4(+) cell counts >350 cells/mm3. Vaccine 33: 1890-1896.