Can immunization with Bacillus Calmette-Guérin be improved for prevention or therapy and elimination of chronic Mycobacterium tuberculosis infection?

References

• Furin J, Cox H, Pai M. Tuberculosis. Lancet. 2019;393:1642–1656.
   PubMed Web of Science ®Google Scholar
• Mishra A, Surolia A. Mycobacterium tuberculosis: surviving and indulging in an unwelcoming host. IUBMB Life. 2018;70:917–925.
   PubMed Web of Science ®Google Scholar
• Khan A, Rebhan A, Seminara D, et al. Enduring challenge of latent tuberculosis in older nursing home residents: A brief review. J Clin Med Res. 2019;11:385–390.
   PubMedGoogle Scholar
• Gengenbacher M, Kaufmann SHE. Mycobacterium tuberculosis: success through dormancy. FEMS Microbiol Rev. 2012;36:514–532.
   PubMed Web of Science ®Google Scholar
• Coppola M, Ottenhoff TH. Genome wide approaches discover novel Mycobacterium tuberculosis antigens as correlates of infection, disease, immunity and targets for vaccination. Semin Immunol. 2018;39:88–101.
   PubMed Web of Science ®Google Scholar
• Moliva JI, Turner J, Torrelles JB. Prospects in Mycobacterium bovis Bacille Calmette et Guérin (BCG) vaccine diversity and delivery: why does BCG fail to protect against tuberculosis? Vaccine. 2015;33:5035–5041.
   PubMed Web of Science ®Google Scholar
• Gengenbacher M, Niewenhuizen NE, Kaufmann SHE. BCG – old workhorse, new skills. Curr Opin Immunol. 2017;47:8–16.
   PubMed Web of Science ®Google Scholar
• Kaufmann SHE, Weiner J, von Reyn CF. Novel approaches to tuberculosis vaccine development. Int J Infect Dis. 2017;56:263–267.
   PubMed Web of Science ®Google Scholar
• Fine PEM, Carneiro IAM, Milstien JB, et al. Issues relating to the use of BCG in immunization programmes: a discussion document. [WHO/V&B/99.23] Author’s manuscript. World Health Organization; 1999. Available from: https://apps.who.int/iris/handle/10665/66120
   Google Scholar
• Orme IM. Vaccine development for tuberculosis: current progress. Drugs. 2013;73:1015–1024.
   PubMed Web of Science ®Google Scholar
• Araujo LS, da Silva N de B, da Silva RJ, et al. Profile of interferon-gamma response to latency-associated and novel in vivo expressed antigens in a cohort of subjects recently exposed to Mycobacterium tuberculosis. Tuberculosis. 2015;95:751–757.
   PubMedGoogle Scholar
• Cohen A, Mathiasen VD, Schön T, et al. The global prevalence of latent tuberculosis: a systematic review and meta-analysis. Eur Respir J. 2019;54:1900655.
   PubMed Web of Science ®Google Scholar
• Barrios-Payán J, Saqui-Salces M, Jeyanathan M, et al. Extrapulmonary locations of Mycobacterium tuberculosis DNA during latent infection. J Infect Dis. 2012;206:1194–1205.
   PubMed Web of Science ®Google Scholar
• Goscé L, Bitencourt J, Gupta RK, et al. BCG vaccination following latent TB treatment: possible implications for different settings. Int J Infect Dis. 2019;80:S17–S19.
   Web of Science ®Google Scholar
• Nemes E, Geldenhuys H, Rozot V, et al. Prevention of M. tuberculosis infection with H4: IC31vaccine or BCG revaccination. N Engl J Med. 2018;379:138–149.
   PubMed Web of Science ®Google Scholar
• Suliman S, Geldenhuys H, Johnson JL, et al. Bacillus Calmette-Guérin (BCG) revaccination of adults with latent Mycobacterium tuberculosis infection induces long-lived BCG-reactive NK cell responses. J Immunol. 2016;197:1100–1110.
   PubMed Web of Science ®Google Scholar
• Pedroza-Roldán C, Guapillo C, Barrios-Payán, et al. The BCGΔBCG1419c strain, which produces more pellicle in vitro, improves control of chronic tuberculosis in vivo. Vaccine. 2016;34:4763–4770.
   PubMed Web of Science ®Google Scholar
• Sathkumara HD, Pai S, Acevez-Sánchez MJ, et al. BCG vaccination prevents reactivation of latent lymphatic murine tuberculosis independently of CD4+ T cells. Front Immunol. 2019;10:532.
   PubMed Web of Science ®Google Scholar
• Verrall AJ, Alisjahbana B, Apriani L, et al. Early clearance of Mycobacterium tuberculosis: the INFECT case contact cohort study in Indonesia. J Infect Dis. 2019. DOI:10.1093/infdis/jiz168.
   Google Scholar
• Fox GJ, Menzies D. Epidemiology of tuberculosis immunology. The new paradigm of immunology to tuberculosis. New York (NY): Springer; 2013.
   Google Scholar
• Wayne LG, Shoaskey CD. Nonreplicating persistence of Mycobacterium tuberculosis. Annu Rev Microbiol. 2001;55:139–163.
   PubMed Web of Science ®Google Scholar
• Voskuil MI, Schnappinger D, Visconti KC, et al. Inhibition of respiration by nitric oxide induces a Mycobacterium tuberculosis dormancy program. J Exp Med. 2003;5:705–713.
   Google Scholar
• Lin PL, Flynn JL. Understanding latent tuberculosis: a moving target. J Immunol. 2010;185:15–22.
   PubMed Web of Science ®Google Scholar
• Hunter RL. Tuberculosis as a three-act play: A new paradigm for the pathogenesis of pulmonary tuberculosis. Tuberculosis. 2016;97:8–17.
   PubMed Web of Science ®Google Scholar
• Chan J, Flynn J. The immunological aspects of latency in tuberculosis. Clin Immunol. 2004;110:2–12.
   PubMed Web of Science ®Google Scholar
• Theron G, Peter J, Lenders L, et al. Correlation of Mycobacterium tuberculosis specific and non-specific quantitative Th1 T-cell responses with bacillary load in a high burden setting. PLoS ONE. 2012;7:e37436.
   PubMedGoogle Scholar
• Meier NR, Jacobsen M, Ottenhoff THM, et al. A systematic review on novel Mycobacterium tuberculosis antigens and its discriminatory potential for the diagnosis of latent and active tuberculosis. Front Immunol. 2018;9:2476.
   PubMedGoogle Scholar
• Salgame P, Geadas C, Collins L, et al. Latent tuberculosis infection – revisiting and revising concepts. Tuberculosis. 2015;95:373–384.
   PubMed Web of Science ®Google Scholar
• Duffy FJ, Weiner J, Hansen S, et al. Immunometabolic signatures predict risk of progression to active tuberculosis and disease outcome. Front Immunol. 2019;10:527.
   PubMed Web of Science ®Google Scholar
• Berry MP, Graham CM, McNab FW, et al. An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis. Nature. 2010;466:973–977.
   PubMed Web of Science ®Google Scholar
• Singhania A, Verma R, Graham CM, et al. A modular transcriptional signature identifies phenotypic heterogeneity of human tuberculosis infection. Nat Commun. 2018;9:2308.
   PubMed Web of Science ®Google Scholar
• Boon C, Dick T. How Mycobacterium tuberculosis goes to sleep: the dormancy survival regulator DosR a decade later. Future Microbiol. 2012;7:513–518.
   PubMed Web of Science ®Google Scholar
• Shi L, Jung YJ, Tyagi S, et al. Expression of Th1-mediated immunity in mouse lungs induces a Mycobacterium tuberculosis transcription pattern characteristic of nonreplicating persistence. Proc Natl Acad Sci USA. 2003;100:241–246.
   PubMed Web of Science ®Google Scholar
• Leistikow RL, Morton RA, Bartek IL, et al. The Mycobacterium tuberculosis DosR regulon assists in metabolic homeostasis and enables rapid recovery from nonrespiring dormancy. J Bacteriol. 2010;192:1662–1670.
   PubMed Web of Science ®Google Scholar
• Commandeur S, Lin MY, van Meijgaarden KE, et al. Double- and monofunctional CD4+ and CD8+ T-cell responses to Mycobacterium tuberculosis DosR antigens and peptides in long-term latently infected individuals. Eur J Immunol. 2011;41:2925–2936.
   PubMed Web of Science ®Google Scholar
• Taylor JL, Wieczorek A, Keyser AR, et al. HspX-mediated protection against tuberculosis depends on its chaperoning of a mycobacterial molecule. Immunol Cell Biol. 2012;90:945–954.
   PubMed Web of Science ®Google Scholar
• Singh S, Saraav I, Sharma S. Immunogenic potential of latency associated antigens against Mycobacterium tuberculosis. Vaccine. 2014;32:712–716.
   PubMed Web of Science ®Google Scholar
• Serra-Vidal MM, Latorre I, Franken KL, et al. Immunogenicity of 60 novel latency-related antigens of Mycobacterium tuberculosis. Front Microbiol. 2014;5:1–13.
   PubMed Web of Science ®Google Scholar
• Jiménez BA, Hinojoza-Loza E, Flores-Valdez MA, et al. Expression of non-replicating persistence associated genes of Mycobacterium bovis in lymph nodes from skin test-reactor cattle. Microb Pathog. 2013;61–62:23–28.
   PubMed Web of Science ®Google Scholar
• Alvarez AH, Gutiérrez-Ortega A, Gómez-Entzin V, et al. Assessment of antigenic supplementation of bovine purified protein derivative for diagnosis of subclinical infection with Mycobacterium bovis in cattle. Microb Pathog. 2017;108:114–121.
   PubMed Web of Science ®Google Scholar
• Singh S, Bhatt P, Sharma M, et al. Immunogenicity of late stage specific peptide antigens of Mycobacterium tuberculosis. Infect Genet Evol. 2019;74:103930.
   PubMed Web of Science ®Google Scholar
• Pandey K, Singh S, Bhatt P, et al. DosR proteins of Mycobacterium tuberculosis upregulate effector T cells and down regulate T regulatory cells in TB patients and their healthy contacts. Microb Pathog. 2019;126:399–406.
   PubMed Web of Science ®Google Scholar
• Rakshit S, Adiga V, Nayak S, et al. Circulating Mycobacterium tuberculosis DosR latency-antigen specific, polyfunctional, regulatory IL10+Th17 CD4 T-cells differentiate latent from active tuberculosis. Sci Rep. 2017;7:11948.
   PubMed Web of Science ®Google Scholar
• Selvaraj S, Sambandam V, Sardar D, et al. In silico analysis of DosR regulon proteins of Mycobacterium tuberculosis. Gene. 2012;506:233–241.
   PubMed Web of Science ®Google Scholar
• Lin MY, Geluk A, Smith SG, et al. Lack of immune responses to Mycobacterium tuberculosis DosR regulon proteins following Mycobacterium bovis BCG vaccination. Infect Immun. 2007;75:3523–3530.
   PubMed Web of Science ®Google Scholar
• Dey B, Jain R, Gupta UD, et al. A booster vaccine expressing a latency-associated antigen augments BCG induced immunity and confers enhanced protection against tuberculosis. PLoS One. 2011;6:e23360.
   PubMed Web of Science ®Google Scholar
• Siddiqui KF, Amir M, Khan N, et al. Prime-boost vaccination strategy with bacillus Calmette-Guérin (BCG) and liposomized alpha-crystalline alpha1 reinvigorates BCG potency. Clin Exp Immunol. 2015;181:286–296.
   PubMed Web of Science ®Google Scholar
• Chiliza TE, Pillay M, Naidoo K, et al. Immunoscreening of the M. tuberculosis F15/LAM4/KZM secretome library against TB patients’ sera identifies unique active- and latent-TB specific biomarkers. Tuberculosis. 2019;115:161–170.
   PubMed Web of Science ®Google Scholar
• Flores-Valdez MA. New potential biomarkers to assess efficacy of protection afforded by vaccine candidates against tuberculosis. Clin Microbiol Infect. 2019;25:656–658.
   PubMed Web of Science ®Google Scholar
• Singh AK, Gupta UD. Animal models of tuberculosis: lessons learnt. Ind J Med Res. 2018;147:456–463.
   PubMed Web of Science ®Google Scholar
• Chen Y, Chao Y, Deng Q, et al. Potential challenges to the Stop TB Plan for humans in China; cattle maintain M. bovis and M. tuberculosis. Tuberculosis. 2009;89:95–100.
   PubMed Web of Science ®Google Scholar
• Waters WR, Palmer MV, Thacker TC, et al. Tuberculosis immunity: opportunity from studies with cattle. Clin Dev Immunol. 2011;2011:768542.
   PubMedGoogle Scholar
• Naranjo V, Gortazar C, Villar M, et al. Comparative genomics and proteomics to study tissue-specific response and function in natural Mycobacterium bovis infections. Anim Health Res Rev. 2007;8:81–88.
   PubMedGoogle Scholar
• Palmer MV, Thacker TC, Waters WR. Differential cytokine gene expression in granulomas from lungs and lymph nodes of cattle experimentally infected with aerosolized Mycobacterium bovis. PLoS One. 2016;11:e0167471.
   PubMed Web of Science ®Google Scholar
• Palmer MV, Thacker TC, Waters WR, et al. Persistence of Mycobacterium bovis Bacillus Calmette-Guérin in white-tailed deer (Odocoileus virginianus) after oral or parenteral vaccination. Zoonoses Public Health. 2010;57:e206–e212.
   PubMed Web of Science ®Google Scholar
• Mendum TA, Chandran A, Williams K, et al. Transposon libraries identify novel Mycobacterium bovis BCG genes involved in the dynamic interactions required for BCG to persist during in vivo passage in cattle. BMC Genomics. 2019;20:431.
   PubMed Web of Science ®Google Scholar
• Alvarez AH, Flores MA. Are cattle a surrogate model for pathogenic mycobacterial latent infection? J Mycob Dis. 2014;4:4.
   Google Scholar
• Van Rhijn I, Godfroid J, Michel A, et al. Bovine tuberculosis as a model for human tuberculosis: advantages over small animal models. Microbes Infect. 2008;10:711–715.
   PubMed Web of Science ®Google Scholar
• Jones GJ, Pirson C, Gideon HP, et al. Immune responses to the enduring hypoxic response antigen Rv0188 are preferentially detected in Mycobacterium bovis infected cattle with low pathology. PLoS One. 2011;6:e21371.
   PubMed Web of Science ®Google Scholar
• Arriaga AK, Orozco EH, Aguilar LD, et al. Immunological and pathological comparative analysis between experimental latent tuberculosis infection and progressive pulmonary tuberculosis. Clin Exp Immunol. 2002;128:229–237.
   PubMed Web of Science ®Google Scholar
• Dutta NK, Illei PB, Jain SK, et al. Characterization of a novel necrotic granuloma model of latent tuberculosis infection and reactivation in mice. Am J Pathol. 2014;184:2045–2055.
   PubMed Web of Science ®Google Scholar
• Pedroza-Roldán C, Flores-Valdez MA. Recent mouse models and vaccine candidates for preventing chronic/latent tuberculosis infection and its reactivation. Pathog Dis. 2017;75:1–5.
   Web of Science ®Google Scholar
• Campuzano J, Aguilar D, Arriaga K, et al. The PGRS domain of Mycobacterium tuberculosis PE_PGRS Rv1759c antigen is an efficient subunit vaccine to prevent reactivation in a murine model of chronic tuberculosis. Vaccine. 2007;25:3722–3729.
   PubMed Web of Science ®Google Scholar
• Liang Y, Zhang X, Bai X, et al. Immunogenicity and therapeutic effects of latency-associated genes in a Mycobacterium tuberculosis reactivation mouse model. Hum Gene Ther Methods. 2019;30:60–69.
   PubMed Web of Science ®Google Scholar
• Kong H, Dong C, Xiong S. A novel vaccine p846 encoding Rv3615c, Mtb10.4, and Rv2660c elicits robust immune response and alleviates lung injury induced by Mycobacterium infection. Hum Vaccine Immunother. 2014;10:378–390.
   PubMed Web of Science ®Google Scholar
• Veatch AV, Kaushal D. Opening Pandora’s box: mechanisms of Mycobacterium tuberculosis resuscitation. Trends Microbiol. 2018;26:145–157.
   PubMed Web of Science ®Google Scholar
• Kondratieva TK, Kapina MA, Rubakova EI, et al. A new model for chronic and reactivation tuberculosis: infection with genetically attenuated Mycobacterium tuberculosis in mice with polar susceptibility. Tuberculosis. 2018;113:130–138.
   PubMed Web of Science ®Google Scholar
• Commandeur S, van Meijgaarden KE, Lin MY, et al. Identification of human T-cell responses to Mycobacterium tuberculosis resuscitation-promoting factors in long-term latently infected individuals. Clin Vaccine Immunol. 2011;18:676–683.
   PubMed Web of Science ®Google Scholar
• Kapoor N, Pawar S, Sirakova TD, et al. Human granuloma in vitro model, for TB dormancy and resuscitation. PLoS One. 2013;8:e53657.
   PubMed Web of Science ®Google Scholar
• KJ D, VV M, MO S, et al. Mutants of Mycobacterium tuberculosis lacking three of the five rpf-like genes are defective for growth in vivo and for resuscitation in vitro. Infect Immun. 2005;73:3038–3043.
   PubMed Web of Science ®Google Scholar
• Nikitushkin VD, Demina G, Kaprelyants AS. Rpf proteins are the factors of reactivation of the dormant forms of actinobacteria. Biochemistry. 2016;81:1719–1734.
   PubMed Web of Science ®Google Scholar
• Rosser A, Stover C, Pareek M, et al. Resuscitation-promoting factors are important determinants of the pathophysiology in Mycobacterium tuberculosis infection. Crit Rev Microbiol. 2017;43:621–630.
   PubMed Web of Science ®Google Scholar
• Marongiu L, Donini M, Toffali L, et al. ESAT-6 and HspX improve the effectiveness of BCG to induce human dendritic cells-dependent Th1 and NK cells activation. PLoS One. 2013;8:e75684.
   PubMed Web of Science ®Google Scholar
• Su H, Zhu S, Zhu L, et al. Mycobacterium tuberculosis latent antigen Rv2029c from the multistage DNA vaccine A39 drives TH1 responses via TLR-mediated macrophage activation. Front Microbiol. 2017;8:2266.
   PubMed Web of Science ®Google Scholar
• Yuan X, Teng X, Jing Y, et al. A live attenuated BCG vaccine overexpressing multistage antigens Ag85B and HspX provides superior protection against Mycobacterium tuberculosis infection. Appl Microbiol Biotechnol. 2015;99:10587–10595.
   PubMed Web of Science ®Google Scholar
• Li F, Kang H, Li J, et al. Subunit vaccines consisting of antigens from dormant and replicating bacteria show promising therapeutic effect against Mycobacterium bovis BCG latent infection. Scand J Immunol. 2017;85:425–432.
   PubMed Web of Science ®Google Scholar
• Gengenbacher M, Kaiser P, Schuerer S, et al. Post-exposure vaccination with the vaccine candidate Bacillus Calmette-Guérin ΔureC:: hly induces superior protection in a mouse model of subclinical tuberculosis. Microbes Infect. 2016;18:364–368.
   PubMed Web of Science ®Google Scholar
• Reece ST, Nasser-Eddine A, Dietrich J, et al. Improved long-term protection against Mycobacterium tuberculosis Beijing/W in mice after intra-dermal inoculation of recombinant BCG expressing latency associated antigens. Vaccine. 2011;29:8740–8744.
   PubMed Web of Science ®Google Scholar
• Aagaard C, Hoang T, Dietrich J, et al. A multistage tuberculosis vaccine that confers efficient protection before and after exposure. Nat Med. 2011;17:189–194.
   PubMed Web of Science ®Google Scholar
• Wieczorek AE, Troudt JL, Knabenbauer P, et al. HspX vaccination and role in virulence in the guinea pig model of tuberculosis. Pathog Dis. 2014;71:315–325.
   PubMed Web of Science ®Google Scholar
• Conoupas C, Pinto R, Nagalingam G, et al. Mycobacterium tuberculosis components expressed during chronic infection of the lung contribute to long-term control of pulmonary tuberculosis in mice. NPJ Vacc. 2016;1:16012.
   PubMed Web of Science ®Google Scholar
• Khademi F, Derakhshan M, Yousefi-Avarvand A, et al. Multi-stage subunit vaccines against Mycobacterium tuberculosis: an alternative to the BCG vaccine or a BCG-prime boost? Expert Rev Vaccines. 2018;17:31–44.
   PubMed Web of Science ®Google Scholar
• Peña JC, Ho WZ. Non-human primate models of tuberculosis. Microbiol Spectr. 2016. DOI:10.1128/microbiolspec.TBTB2-0007-2016
   PubMed Web of Science ®Google Scholar
• Flynn JL, Gideon HP, Mattila JT, et al. Immunology studies in non-human primate models of tuberculosis. Immunol Rev. 2015;264:60–73.
   PubMed Web of Science ®Google Scholar
• Capuano SV 3rd, Croix DA, Pawar S, et al. Experimental Mycobacterium tuberculosis infection of cynomolgus macaques closely resembles the various manifestations of human M. tuberculosis infection. Infect Immun. 2003;71:5831–5844.
   PubMed Web of Science ®Google Scholar
• Lin PL, Rodgers M, Smith L, et al. Quantitative comparison of active and latent tuberculosis in the cynomolgus macaque model. Infect Immun. 2009;77:4631–4642.
   PubMed Web of Science ®Google Scholar
• Gormus BJ, Blanchard JL, Alvarez XH, et al. Evidence for a rhesus monkey model of asymptomatic tuberculosis. J Med Primatol. 2004;33:134–145.
   PubMed Web of Science ®Google Scholar
• Lin PL, Myers A, Smith L, et al. 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. 2010;62:340–350.
   PubMed Web of Science ®Google Scholar
• Diedrich CR, Mattila JT, Klein E, et al. Reactivation of latent tuberculosis in cynomolgus macaques infected with SIV is associated with early peripheral T cell depletion and not virus load. PLoS One. 2010;5:e9611.
   PubMed Web of Science ®Google Scholar
• Lin PL, Rutledge T, Green AM, et al. CD4 T cell depletion exacerbates acute Mycobacterium tuberculosis while reactivation of latent infection is dependent on severity of tissue depletion in cynomolgus macaques. AIDS Res Hum Retroviruses. 2012;28:1693–1702.
   PubMed Web of Science ®Google Scholar
• Mehra S, Golden NA, Dutta NK, et al. Reactivation of latent tuberculosis in rhesus macaques by coinfection with simian immunodeficiency virus. J Med Primatol. 2011;40:233–243.
   PubMed Web of Science ®Google Scholar
• Foreman TW, Mehra S, LoBato DN, et al. CD4+ T-cell-independent mechanisms suppress reactivation of latent tuberculosis in a macaque model of HIV coinfection. Proc Natl Acad Sci USA. 2016;113:E5636–E5644.
   PubMed Web of Science ®Google Scholar
• Kuroda MJ, Sugimoto C, Cai Y, et al. High turnover of tissue macrophages contributes to tuberculosis reactivation in simian immunodeficiency virus-infected rhesus macaques. J Infect Dis. 2018;217:1865–1874.
   PubMed Web of Science ®Google Scholar
• Sharpe S, White A, Gleeson F, et al. Ultra low 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
• Lin PL, Dietrich J, Tan E, et al. 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. 2012;122:303–314.
   PubMed Web of Science ®Google Scholar
• Darrah PA, DiFazio RM, Maiello P, et al. Boosting BCG with proteins or rAd5 does not enhance protection against tuberculosis in rhesus macaques. NPJ Vaccines. 2019;4:21.
   PubMed Web of Science ®Google Scholar
• Leung-Theung-Long S, Gouanvic M, Coupet CA, et al. A novel MVA-based multiphasic vaccine for prevention or treatment of tuberculosis induces broad and multifunctional cell-mediated immunity in mice and primates. PLoS One. 2015;10:e0143552.
   PubMed Web of Science ®Google Scholar
• Dockrell HM. Towards new TB vaccines: what are the challenges. Pathog Dis. 2016;74:ftw016.
   PubMed Web of Science ®Google Scholar
• Billeskov R, Elvang TT, Andersen PL, et al. The HyVac4 subunit vaccine efficiently boosts BCG-primed anti-mycobacterial protective immunity. PLoS One. 2012;7:e39909.
   PubMed Web of Science ®Google Scholar
• Wang C, Lu J, Du W, et al. Ag85b/ESAT6-CFP10 adjuvanted with aluminum/poly-IC effectively protects guinea pigs from latent Mycobacterium tuberculosis infection. Vaccine. 2019;37:4477–4484.
   Web of Science ®Google Scholar
• Rai PK, Chodisetti SB, Maurya SK, et al. A lipidated bi-epitope vaccine comprising of MHC-I and MHC-II binder peptides elicits protective CD4 T cell and CD8 T cell immunity against Mycobacterium tuberculosis. J Transl Med. 2018;16:279.
   PubMed Web of Science ®Google Scholar
• Mansury D, Ghazvini K, Amel-Jamehdar S, et al. Enhancement of the effect of BCG vaccine against tuberculosis using DDA/TDB liposomes containing a fusion protein of HspX, PPE44, and EsxV. Artif Cells Nanomed Biotechnol. 2019;47:370–377.
   PubMed Web of Science ®Google Scholar
• Soleimanpour S, Farsiani H, Mosavat A, et al. APC targeting enhances immunogenicity of a novel multistage Fc-fusion tuberculosis vaccine in mice. Appl Microbiol Biotechnol. 2015;99:10467–10480.
   PubMed Web of Science ®Google Scholar
• Mosavat A, Soleimanpour S, Farsiani H, et al. Fused Mycobacterium tuberculosis multi-stage immunogens with an Fc-delivery system as a promising approach for the development of a tuberculosis vaccine. Infect Genet Evol. 2016;39:163–172.
   PubMed Web of Science ®Google Scholar
• Khademi F, Derakhshan M, Yousefi-Avarvand A, et al. A novel antigen of Mycobacterium tuberculosis and MPLA adjuvant co-entrapped into PLGA:DDA hybrid nanoparticles stimulates mucosal and systemic immunity. Microb Pathog. 2018;125:507–513.
   PubMed Web of Science ®Google Scholar
• Arroyo L, Rojas M, Ortíz BL, et al. Dynamics of the T cell response to Mycobacterium tuberculosis DosR and Rpf antigens in a colombian population of household contacts of recently diagnosed pulmonary tuberculosis patients. Tuberculosis. 2016;97:97–107.
   PubMed Web of Science ®Google Scholar
• Andersen P, Scriba TJ. Moving tuberculosis vaccines from theory to practice. Nat Rev Immunol. 2019;19:550–562.
   PubMed Web of Science ®Google Scholar
• Ma J, Teng X, Wang X, et al. A multistage subunit vaccine effectively protects mice against primary progressive tuberculosis, latency and reactivation. EBioMedicine. 2017;22:143–154.
   PubMed Web of Science ®Google Scholar
• Coppola M, van den Eeden SJ, Wilson L, et al. Synthetic long peptide derived from Mycobacterium tuberculosis latency antigen Rv1733c protects against tuberculosis. Clin Vaccine Immunol. 2015;22:1060–1069.
   PubMedGoogle Scholar