Tuberculosis vaccines

{{Short description|Vaccines to prevent tuberculosis}}

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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.{{Cite journal |last1=Prabowo |first1=Satria A. |last2=Gröschel |first2=Matthias I. |last3=Schmidt |first3=Ed D. L. |last4=Skrahina |first4=Alena |last5=Mihaescu |first5=Traian |last6=Hastürk |first6=Serap |last7=Mitrofanov |first7=Rotislav |last8=Pimkina |first8=Edita |last9=Visontai |first9=Ildikó |last10=de Jong |first10=Bouke |last11=Stanford |first11=John L. |last12=Cardona |first12=Père-Joan |last13=Kaufmann |first13=Stefan H. E. |last14=van der Werf |first14=Tjip S. |date=2013-04-01 |title=Targeting multidrug-resistant tuberculosis (MDR-TB) by therapeutic vaccines |url=https://link.springer.com/article/10.1007/s00430-012-0278-6 |journal=Medical Microbiology and Immunology |language=en |volume=202 |issue=2 |pages=95–104 |doi=10.1007/s00430-012-0278-6 |issn=1432-1831}} As of 2021, the only effective tuberculosis vaccine in common use is the Bacillus Calmette-Guérin (BCG) vaccine, first used on humans in 1921.{{Cite journal |last1=White |first1=A. D. |last2=Sibley |first2=L. |last3=Dennis |first3=M. J. |last4=Gooch |first4=K. |last5=Betts |first5=G. |last6=Edwards |first6=N. |last7=Reyes-Sandoval |first7=A. |last8=Carroll |first8=M. W. |last9=Williams |first9=A. |last10=Marsh |first10=P. D. |last11=McShane |first11=H. |last12=Sharpe |first12=S. A. |date=May 2013 |title=Evaluation of the Safety and Immunogenicity of a Candidate Tuberculosis Vaccine, MVA85A, Delivered by Aerosol to the Lungs of Macaques |journal=Clinical and Vaccine Immunology |volume=20 |issue=5 |pages=663–672 |doi=10.1128/CVI.00690-12 |pmc=3647747 |pmid=23446219}}{{cite journal | vauthors = McShane H | title = Tuberculosis vaccines: beyond bacille Calmette-Guerin | journal = Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences | volume = 366 | issue = 1579 | pages = 2782–89 | date = October 2011 | pmid = 21893541 | pmc = 3146779 |doi-access=free | doi = 10.1098/rstb.2011.0097 }}{{cite web |title=Vaccines {{!}} Basic TB Facts |url=https://www.cdc.gov/tb/topic/basics/vaccines.htm |date=16 June 2021 |publisher=CDC |access-date=30 December 2021 |archive-date=30 December 2021 |archive-url=https://web.archive.org/web/20211230115301/https://www.cdc.gov/tb/topic/basics/vaccines.htm |url-status=live }} 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{{Cite journal |last1=Oksanen |first1=Kaisa E. |last2=Halfpenny |first2=Nicholas J. A. |last3=Sherwood |first3=Eleanor |last4=Harjula |first4=Sanna-Kaisa E. |last5=Hammarén |first5=Milka M. |last6=Ahava |first6=Maarit J. |last7=Pajula |first7=Elina T. |last8=Lahtinen |first8=Marika J. |last9=Parikka |first9=Mataleena |last10=Rämet |first10=Mika |date=2013-10-25 |title=An adult zebrafish model for preclinical tuberculosis vaccine development |url=https://linkinghub.elsevier.com/retrieve/pii/S0264410X1301205X |journal=Vaccine |volume=31 |issue=45 |pages=5202–5209 |doi=10.1016/j.vaccine.2013.08.093 |pmid=24055305 |issn=0264-410X|url-access=subscription }} (including defence against TB meningitis and miliary TB),{{Cite journal |last1=Hussey |first1=Gregory |last2=Hawkridge |first2=Tony |last3=Hanekom |first3=Willem |date=2007-06-01 |title=Childhood tuberculosis: old and new vaccines |url=https://linkinghub.elsevier.com/retrieve/pii/S1526054207000401 |journal=Paediatric Respiratory Reviews |volume=8 |issue=2 |pages=148–154 |doi=10.1016/j.prrv.2007.04.009 |pmid=17574159 |issn=1526-0542|url-access=subscription }}{{Cite journal |last1=Verma |first1=Indu |last2=and Grover |first2=Ajay |date=2009-11-01 |title=Antituberculous vaccine development: a perspective for the endemic world |url=https://www.tandfonline.com/doi/full/10.1586/erv.09.111 |journal=Expert Review of Vaccines |volume=8 |issue=11 |pages=1547–1553 |doi=10.1586/erv.09.111 |issn=1476-0584 |pmid=19863247|url-access=subscription }} its efficacy in adults is variable,{{Cite journal |date=1996-07-06 |title=Randomised controlled trial of single BCG, repeated BCG, or combined BCG and killed Mycobacterium leprae vaccine for prevention of leprosy and tuberculosis in Malawi. Karonga Prevention Trial Group |url=https://pubmed.ncbi.nlm.nih.gov/8691924 |journal=Lancet |volume=348 |issue=9019 |pages=17–24 |doi=10.1016/S0140-6736(96)02166-6 |issn=0140-6736 |pmid=8691924}} ranging from 0% to 80%.{{Cite journal |last1=Tyne |first1=Anneliese S. |last2=Chan |first2=John Gar Yan |last3=Shanahan |first3=Erin R. |last4=Atmosukarto |first4=Ines |last5=Chan |first5=Hak-Kim |last6=Britton |first6=Warwick J. |last7=West |first7=Nicholas P. |date=2013-09-13 |title=TLR2-targeted secreted proteins from Mycobacterium tuberculosis are protective as powdered pulmonary vaccines |url=https://linkinghub.elsevier.com/retrieve/pii/S0264410X13009493 |journal=Vaccine |volume=31 |issue=40 |pages=4322–4329 |doi=10.1016/j.vaccine.2013.07.022 |pmid=23880366 |hdl=1885/66093 |issn=0264-410X|hdl-access=free }} Several variables have been considered as responsible for the varying outcomes. Demand for TB immunotherapy advancement exists because the disease has become increasingly drug-resistant.

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{{Cite journal |last1=Horwitz |first1=Marcus A. |last2=Harth |first2=Günter |date=2003 |title=A New Vaccine against Tuberculosis Affords Greater Survival after Challenge than the Current Vaccine in the Guinea Pig Model of Pulmonary Tuberculosis |journal=Infection and Immunity |volume=71 |issue=4 |pages=1672–1679 |doi=10.1128/IAI.71.4.1672-1679.2003 |issn=0019-9567 |pmid=12654780|pmc=152073 }} and phase I human trials in 2008.{{Cite journal |last1=Hoft |first1=Daniel F. |last2=Blazevic |first2=Azra |last3=Abate |first3=Getahun |last4=Hanekom |first4=Willem A. |last5=Kaplan |first5=Gilla |last6=Soler |first6=Jorge H. |last7=Weichold |first7=Frank |last8=Geiter |first8=Larry |last9=Sadoff |first9=Jerald C. |last10=Horwitz |first10=Marcus A. |date=2008-11-15 |title=A new recombinant bacille Calmette-Guérin vaccine safely induces significantly enhanced tuberculosis-specific immunity in human volunteers |journal=The Journal of Infectious Diseases |volume=198 |issue=10 |pages=1491–1501 |doi=10.1086/592450 |issn=0022-1899 |pmc=2670060 |pmid=18808333}}
• MTBVAC,{{cite journal |last1=Arbuesab |first1=Ainhoa |last2=Aguilo |first2=Juan I. |last3=Gonzalo-Asensio |first3=Jesus |last4=Marinova |first4=Dessislava |last5=Uranga |first5=Santiago |last6=Puentes |first6=Eugenia |last7=Fernandez |first7=Conchita |last8=Parra |first8=Alberto |last9= Cardona |first9=Pere Joan |last10=Vilaplana |first10=Cristina |last11=Ausin |first11=Vicente |last12=Williams |first12=Ann |last13=Clark |first13=Simon |last14=Malaga |first14=Wladimir |last15=Guilhoth |first15=Christophe |last16=Gicquel |first16=Brigitte |last17=Martin |first17=Carlos |date=1 October 2013 |title=Construction, characterization and preclinical evaluation of MTBVAC, the first live-attenuated M. tuberculosis-based vaccine to enter clinical trials |url=http://zaguan.unizar.es/record/61676 |journal=Vaccine |volume=31 |number=42 |pages=4867–4873 |doi=10.1016/j.vaccine.2013.07.051 |pmid=23965219|s2cid=6225547 |url-access=subscription }} 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.{{Cite journal |last1=Martín |first1=Carlos |last2=Marinova |first2=Dessislava |last3=Aguiló |first3=Nacho |last4=Gonzalo-Asensio |first4=Jesús |date=2021-12-08 |title=MTBVAC, a live TB vaccine poised to initiate efficacy trials 100 years after BCG |journal=Vaccine |series=100 Years of the Bacillus Calmette-Guérin Vaccine |volume=39 |issue=50 |pages=7277–7285 |doi=10.1016/j.vaccine.2021.06.049 |pmid=34238608 |s2cid=235777018 |issn=0264-410X|doi-access=free }}{{Cite web |title=NCT04975178 |url=https://www.clinicaltrials.gov/study/NCT04975178 |access-date=2023-10-27 |website=www.clinicaltrials.gov}}
• 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.{{Cite journal |last=Tozer |first=Lilly |date=2023-06-28 |title=Promising tuberculosis vaccine gets US$550-million shot in the arm |url=https://www.nature.com/articles/d41586-023-02171-x |journal=Nature |language=en |doi=10.1038/d41586-023-02171-x|pmid=37380847 |s2cid=259285120 |url-access=subscription }}
• 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).