TB Vaccine: Current Scenario and Future Possibilities
Abstract:
Tuberculosis (TB) caused by Mycobacterium tuberculosis has been a major global health challenge for a very long time, especially in low-income countries. It affects more than 10 million people annually and has caused about 1.25 billion deaths in 2023. Bacille Calmette-Guerin (BCG) has been the only vaccine used for the last century. Still, its effectiveness varies widely, particularly in protecting adults and adolescents from the Pulmonary form of TB, necessitating the importance of better and improved vaccines. The emergence of drug-resistant TB, like MDR-TB (multidrug-resistant TB and XDR-TB (extensively drug-resistant TB, has made the situation even more serious. Nearly nineteen new TB vaccines are in clinical trials, with several already in phase 3 trials. MTBVAC is a live attenuated vaccine derived from M. tuberculosis by deletions of phoP and fadD26 virulence genes. This vaccine has shown better immunogenicity and safety and is currently being tested in HIV-negative infants in Sub-Saharan Africa. Recombinant BCG vaccine VPM1002, which expresses listeriolysin O, has shown superior protection and immune response in preclinical studies and is in Phase 3 trials. A subunit vaccine, GamTBvac, combining Ag85A and ESAT-6/CFP-10 antigens with a dextran/CpG adjuvant, has shown strong Th1 and humoral responses. Currently, this vaccine is in Phase 3 trials. With the use of Mycobacterium indicus pranii and Mycobacterium vaccae, the effectiveness of chemotherapy could be increased manifold, thus proving itself to be a potential candidate for tuberculosis. All these developments thus highlight the need for increasing the funding, commitment, and human resources for the production of the TB vaccine, which could help control TB in high-risk regions of the world.
KeyWords:
Tuberculosis Vaccine TB elimination Phase III Trials
References:
- WHO Global Tuberculosis Report 2024
- Marinova, D., Gonzalo-Asensio, J., Aguilo, N. & Martin, C. MTBVAC from discovery to clinical trials in tuberculosis-endemic countries. Expert Review of Vaccines,2017, vol. 16, 565–576.Preprint at https://doi.org/10.1080/14760584.2017.1324303(2017)
- Lacámara, S. & Martin, C. MTBVAC: A Tuberculosis Vaccine Candidate Advancing Towards Clinical Efficacy Trials in TB Prevention. Archivos de Bronconeumologia,2023, vol. 59 821–828 Preprint at https://doi.org/10.1016/j.arbres.2023.09.009
- Martín, C., Marinova, D., Aguiló, N. & Gonzalo-Asensio, J. MTBVAC, a live TB vaccine poised to initiate efficacy trials 100 years after BCG. Vaccine,2021,39, 7277–7285.
- Lai, R., Ogunsola, A. F., Rakib, T. & Behar, S. M. Key advances in vaccine development for tuberculosis—success and challenges,2023, NPJ Vaccines 8,158. https://doi.org/10.1038/s41541-023-00750-7
- Lacámara, S. & Martin, C. MTBVAC: A Tuberculosis Vaccine Candidate Advancing Towards Clinical Efficacy Trials in TB Prevention. 2023, Archivos de Bronconeumologia,vol. 59 821–828. Preprint at https://doi.org/10.1016/j.arbres.2023.09.009.
- Hoseinpour, R. et al. Tuberculosis vaccine developments and efficient delivery systems: A comprehensive appraisal. 2024, Heliyon vol. 10(4).https://doi.org/10.1016/j.heliyon.2024.e26193
- Barreto, M. L. et al. Causes of variation in BCG vaccine efficacy: Examining evidence from the BCG REVAC cluster randomized trial to explore the masking and the blocking hypotheses. Vaccine,2014, 32, 3759–3764.
- Díaz, C. et al. Comparative Metabolomics between Mycobacterium tuberculosis and the MTBVAC Vaccine Candidate. ACS Infect Dis,2019,5, 1317–1326.
- Broset, E., Martín, C. & Gonzalo-Asensio, J. Evolutionary landscape of the mycobacterium tuberculosis complex from the viewpoint of phoPR: Implications for virulence regulation and application to vaccine development.2015, mBio 6(5),10-1128.
- Pérez, I. et al. The Mycobacterium tuberculosis PhoPR virulence system regulates expression of the universal second messenger c-di-AMP and impacts vaccine safety and efficacy.2022, Mol Ther Nucleic Acids 27, 1235–1248.
- Fletcher, H. A. & Schrager, L. TB vaccine development and the End TB Strategy: Importance and current status. Trans R Soc Trop Med Hyg,2016, 110, 212–218.
- Talwar, G., Singh, P., Atrey, N. & C Gupta, J. Making of a highly useful multipurpose vaccine.2016, J Transl Sci 2,11-12.
- Orme, I. M. Vaccine development for tuberculosis: Current progress. 2013, Drugs 73, 1015–1024..
- Thangaraju, P. et al. Versatile Use of Mycobacterium Indicus Pranii (MIP),2023, Vaccine. Indian J Lepr vol. 95,51-64. http://www.ijl.org.in
- Dogra, S., Jain, S., Sharma, A., Chhabra, S. & Narang, T. Mycobacterium indicus pranii (MIP) vaccine: Pharmacology, indication, dosing schedules, administration, and side effects in clinical practice.2023, Indian Dermatology Online Journal vol. 14 753–761. Preprint at https://doi.org/10.4103/idoj.idoj_360_23.
- Huang, C. Y. & Hsieh, W. Y. Efficacy of Mycobacterium vaccae immunotherapy for patients with tuberculosis: A systematic review and meta-analysis.2017, Hum Vaccin Immunother 13, 1960–1971
- Bourinbaiar, A. S. et al. Phase III, placebo-controlled, randomized, double-blind trial of tableted, therapeutic TB vaccine (V7) containing heat-killed M. vaccae administered daily for one month.2020, J Clin Tuberc Other Mycobact Dis 18, 100141.
- Bouzeyen, R. & Javid, B. Therapeutic Vaccines for Tuberculosis: An Overview. 2022, Frontiers in Immunology vol. 13,878471. Preprint at https://doi.org/10.3389/fimmu.2022.878471.
- Dlugovitzky, D. et al. Immunological consequences of three doses of heat-killed Mycobacterium vaccae in the immunotherapy of tuberculosis.2006, Respir Med 100, 1079–1087.
- Srivastava, S., Dey, S. & Mukhopadhyay, S. Vaccines against Tuberculosis: Where Are We Now? Vaccines,2023, vol. 11 Preprint at https://doi.org/10.3390/vaccines11051013.
- Wang, H. et al. Enhancing TB Vaccine Efficacy: Current Progress on Vaccines, Adjuvants and Immunization Strategies.2024, Vaccines vol. 12(1),38 Preprint at https://doi.org/10.3390/vaccines12010038.
- Zhang, Y., Xu, J. C., Hu, Z. D. & Fan, X. Y. Advances in protein subunit vaccines against tuberculosis.2023, Frontiers in Immunology vol. 14,138586. Preprint at https://doi.org/10.3389/fimmu.2023.1238586
- Tkachuk, A. P. et al. Multi-subunit BCG booster vaccine GamTBvac: Assessment of immunogenicity and protective efficacy in murine and Guinea pig TB models,2017 PLoS One 12(4), e0176784.
- Billeskov, R. et al. High antigen dose is detrimental to post-exposure vaccine protection against tuberculosis.,2018, Front Immunol 8,1973.
- Vasina, D. V. et al. First-in-human trials of gamtbvac, a recombinant subunit tuberculosis vaccine candidate: Safety and immunogenicity assessment,2019, Vaccines 7(4),166.
- Tkachuk, A. P. et al. Safety and immunogenicity of the gamtbvac, the recombinant subunit tuberculosis vaccine candidate: A phase II, multi-center, double-blind, randomized, placebo-controlled study,2020, Vaccines,8(4),652.
- Nieuwenhuizen, N. E. et al. The recombinant bacille Calmette-Guérin vaccine VPM1002: Ready for clinical efficacy testing. 2017, Frontiers in Immunology vol. 8,1147. Preprint at https://doi.org/10.3389/fimmu.2017.01147 (2017).
- Houben, D. et al. ESX-1-mediated translocation to the cytosol controls the virulence of mycobacteria. 2012, Cell Microbiol 14, 1287–1298.
- Bouzeyen, R. & Javid, B. Therapeutic Vaccines for Tuberculosis: An Overview,2022, Frontiers in Immunology vol. 13,878471. Preprint at https://doi.org/10.3389/fimmu.2022.878471.
- Grode, L. et al. Increased vaccine efficacy against tuberculosis of recombinant Mycobacterium bovis bacille Calmette-Guérin mutants that secrete listeriolysin. 2005,Journal of Clinical Investigation 115, 2472–2479.
- Gengenbacher, M., Kaiser, P., Schuerer, S., Lazar, D. & Kaufmann, S. H. E. Post-exposure vaccination with the vaccine candidate Bacillus Calmette–Guérin ΔureC:hly induces superior protection in a mouse model of subclinical tuberculosis.2016, Microbes Infect 18, 364–368.
- Loxton, A. G. et al. Safety and immunogenicity of the recombinant mycobacterium bovis BCG vaccine VPM1002 in HIV-unexposed newborn infants in South Africa.2017, Clinical and Vaccine Immunology 24(2),e00439-16.
- Desel, C. et al. Recombinant BCG ΔureC hly+ induces superior protection over parental bcg by stimulating a balanced combination of type 1 and type 17 cytokine responses,2011, Journal of Infectious Diseases, vol. 204, 1573–1584.
- Blossey, A. M. et al. VPM1002 as Prophylaxis against Severe Respiratory Tract Infections including Coronavirus Disease 2019 in the Elderly: A Phase 3 Randomized, Double-Blind, Placebo-Controlled, Multicenter Clinical Study,2023, Clinical Infectious Diseases 76, 1304–1310.
- Singh, M. et al. PreVenTB trial: Protocol for evaluation of efficacy and safety of two vaccines VPM1002 and Immuvac (Mw) in preventing tuberculosis (TB) in healthy household contacts of newly diagnosed sputum smear-positive pulmonary TB patients: Phase III, randomised, double-blind, three-arm placebo-controlled trial,2024, BMJ Open 14(8),e082916.
- Figl, J. et al. Safety and Immunogenicity of Recombinant Bacille Calmette-Guérin Strain VPM1002 and Its Derivatives in a Goat Model,2023, Int J Mol Sci 24(6),5509.