Tuberculosis vaccines

Tuberculosis vaccines
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Tuberculosis (TB) vaccines are vaccinations intended for the prevention of tuberculosis. Immunotherapy as a defence against TB was first proposed in 1890 by Robert Koch.[1] As of 2021, the only effective tuberculosis vaccine in common use is the Bacillus Calmette-Guérin (BCG) vaccine, first used on humans in 1921.[2][3][4] It consists of attenuated (weakened) strains of the cattle tuberculosis bacillus. It is recommended for babies in countries where tuberculosis is common.

About three out of every 10,000 people who get the vaccine experience side effects, which are usually minor except in severely immuno-depressed individuals. While BCG immunization provides fairly effective protection for infants and young children[5] (including defence against TB meningitis and miliary TB),[6][7] its efficacy in adults is variable,[8] ranging from 0% to 80%.[6][9] Several variables have been considered as responsible for the varying outcomes.[6] Demand for TB immunotherapy advancement exists because the disease has become increasingly drug-resistant.[1]

Other tuberculosis vaccines are at various stages of development, including:

  • MVA85A, a viral vector vaccine that uses an MVA virus engineered to express a tuberculosis bacillus antigen in host cells. Human and animal trials were disappointing.
  • rBCG30 is a version of the BCG vaccine engineered to express a higher amount of a certain antigen. It showed promise in animal tests in 2003[10] and phase I human trials in 2008.[11]
  • MTBVAC,[12] an attenuated form of Myobacterium tuberculosis. Phase II trials were completed in 2021 and 2022; phase III trials began in 2022 and will run until 2029.[13][14]
  • M72/AS01E, consisting of two fused tuberculosis bacillus protein antigens together with the adjuvant AS01. It is intended to prevent tuberculosis in people with a latent infection. Promising phase II trials were completed in 2018 and phase III trials are planned.[15]
  • GamTBVak, A subunit recombinant anti-tuberculosis vaccine for the prevention of pulmonary tuberculosis in adults, which is at the stage of clinical research. It contains Ag85A and ESAT-6-CFP-10 antigens in combination with an adjuvant. Developed by the N. F. Gamalei National Research Center for Epidemiology and Microbiology. As of May 2022, phase III clinical trials are underway, data on phase I/II studies are also published in the ClinicalTrials database. A phase I clinical trial on 12 volunteers confirmed the safety and immunological efficacy of the vaccine.

New vaccines are being developed by the Tuberculosis Vaccine Initiative (TBVI).

  1. ^ a b Prabowo, S. et al. "Targeting multidrug-resistant tuberculosis (MDR-TB) by therapeutic vaccines." Med Microbiol Immunol 202 (2013): 95–1041. Print.
  2. ^ White, A. et al. "Evaluation of the Safety and Immunogenicity of a Candidate Tuberculosis Vaccine, MVA85A, Delivered by Aerosol to the Lungs of Macaques." Clinical and Vaccine Immunology 20 (2013): 663–672. Print.
  3. ^ McShane H (October 2011). "Tuberculosis vaccines: beyond bacille Calmette-Guerin". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 366 (1579): 2782–89. doi:10.1098/rstb.2011.0097. PMC 3146779. PMID 21893541.
  4. ^ "Vaccines | Basic TB Facts". CDC. 16 June 2021. Archived from the original on 30 December 2021. Retrieved 30 December 2021.
  5. ^ Cite error: The named reference Oksanen2013 was invoked but never defined (see the help page).
  6. ^ a b c Hussey, G, T Hawkridge, and W Hanekom. "Childhood Tuberculosis: Old And New Vaccines." Paediatric Respiratory Reviews 8.2 (2007): 148–154. Print.
  7. ^ Verma, Indu, and Ajay Grover. "Antituberculous Vaccine Development: A Perspective For The Endemic World." Expert Review of Vaccines 8.11 (2009): 1547–1553. Print.
  8. ^ Karonga Prevention Trial Group. "Randomised controlled trial of single BCG, repeated BCG, or combined BCG and killed Mycobacterium leprae vaccine for prevention of leprosy and tuberculosis in Malawi." The Lancet 348 (1996): 17–24. Print.
  9. ^ Tyne, A. et al. "TLR2-targeted secreted proteins from Mycobacterium tuberculosis areprotective as powdered pulmonary vaccines." Elsevier 31 (2013): 4322–4329. Print.
  10. ^ Horwitz, Marcus A.; Harth, Günter (2003). "A New Vaccine against Tuberculosis Affords Greater Survival after Challenge than the Current Vaccine in the Guinea Pig Model of Pulmonary Tuberculosis". Infection and Immunity. 71 (4): 1672–1679. doi:10.1128/IAI.71.4.1672-1679.2003. ISSN 0019-9567. PMC 152073. PMID 12654780.
  11. ^ Hoft, Daniel F.; Blazevic, Azra; Abate, Getahun; Hanekom, Willem A.; Kaplan, Gilla; Soler, Jorge H.; Weichold, Frank; Geiter, Larry; Sadoff, Jerald C.; Horwitz, Marcus A. (2008-11-15). "A new recombinant bacille Calmette-Guérin vaccine safely induces significantly enhanced tuberculosis-specific immunity in human volunteers". The Journal of Infectious Diseases. 198 (10): 1491–1501. doi:10.1086/592450. ISSN 0022-1899. PMC 2670060. PMID 18808333.
  12. ^ Arbuesab, Ainhoa; Aguilo, Juan I.; Gonzalo-Asensio, Jesus; Marinova, Dessislava; Uranga, Santiago; Puentes, Eugenia; Fernandez, Conchita; Parra, Alberto; Cardona, Pere Joan; Vilaplana, Cristina; Ausin, Vicente; Williams, Ann; Clark, Simon; Malaga, Wladimir; Guilhoth, Christophe; Gicquel, Brigitte; Martin, Carlos (1 October 2013). "Construction, characterization and preclinical evaluation of MTBVAC, the first live-attenuated M. tuberculosis-based vaccine to enter clinical trials". Vaccine. 31 (42): 4867–4873. doi:10.1016/j.vaccine.2013.07.051. PMID 23965219. S2CID 6225547.
  13. ^ Martín, Carlos; Marinova, Dessislava; Aguiló, Nacho; Gonzalo-Asensio, Jesús (2021-12-08). "MTBVAC, a live TB vaccine poised to initiate efficacy trials 100 years after BCG". Vaccine. 100 Years of the Bacillus Calmette-Guérin Vaccine. 39 (50): 7277–7285. doi:10.1016/j.vaccine.2021.06.049. ISSN 0264-410X. PMID 34238608. S2CID 235777018.
  14. ^ "NCT04975178". www.clinicaltrials.gov. Retrieved 2023-10-27.
  15. ^ Tozer, Lilly (2023-06-28). "Promising tuberculosis vaccine gets US$550-million shot in the arm". Nature. doi:10.1038/d41586-023-02171-x. PMID 37380847. S2CID 259285120.