Using BCG Vaccine to Understand Tuberculosis Infection

Summary

Tuberculosis (TB) is a disease that usually causes an infection in the lungs. The only vaccine to prevent TB is called BCG (Bacillus Calmette-Guérin). BCG contains a live germ similar to Mycobacterium tuberculosis, the germ that causes TB. BCG does not work very well, and TB remains the most common cause of death by infection worldwide. Human challenge models involve exposing healthy volunteers to an infectious disease in a safe and controlled way. This helps researchers understand more about an infectious disease and the body's response and can help develop new vaccines and treatments. The purpose of this study is to set up a human challenge model using BCG to understand how the body responds to this. If our human challenge model works well it may be used to help researchers develop new vaccines and tablets to treat TB in the future. This study will recruit healthy volunteers, of all genders, age 18-50 years. The first part of the study (phase A) will recruit 10 participants. Participants in phase A will receive intradermal injection with BCG into the upper arm at three times the usual dose. On day 14 after BCG the following skin samples will be taken from the BCG site with the use of local anaesthetic: skin swab, microbiopsy, skin scrape and punch biopsy. Participants in this phase of the study will also have blood tests to ensure they are safe to take part and to monitor the immune response to BCG. The overall aim of this part of the study will be to ensure BCG can be isolated (grown in culture and by molecular techniques) from participants' BCG site 14 days after the injection. The investigators aim to test whether BCG can be isolated by punch biopsy and minimally invasive techniques (microbiopsy, skin scrape and skin swab). If the investigators find that they can isolate BCG successfully using the minimally invasive methods of skin sampling and the participants have not experienced any serious adverse events, they can proceed to phase B of the study. In phase B 20 participants will be recruited. These participants will receive BCG as described for phase A. They will then have serial skin samples taken using either microbiopsy, skin scrape or skin swab on days 0, 2, 7, 14 and 28. The focus of this phase of the study is to assess immune responses to intradermal injection at the local (skin), systemic (blood) and respiratory mucosal (nose) compartments. This will involve longitudinal sampling from blood, nose and skin to measure BCG growth and the immune response over time.

Timeline

Start

2023-06-30

Primary completion

2024-03-01

Completion

2024-03-01

Publications

• Background Minassian AM, Ronan EO, Poyntz H, Hill AV, McShane H. Preclinical development of an in vivo BCG challenge model for testing candidate TB vaccine efficacy. PLoS One. 2011;6(5):e19840. doi: 10.1371/journal.pone.0019840. Epub 2011 May 24.
• Background Minassian AM, Satti I, Poulton ID, Meyer J, Hill AV, McShane H. A human challenge model for Mycobacterium tuberculosis using Mycobacterium bovis bacille Calmette-Guerin. J Infect Dis. 2012 Apr 1;205(7):1035-42. doi: 10.1093/infdis/jis012.
• Background Harris SA, Meyer J, Satti I, Marsay L, Poulton ID, Tanner R, Minassian AM, Fletcher HA, McShane H. Evaluation of a human BCG challenge model to assess antimycobacterial immunity induced by BCG and a candidate tuberculosis vaccine, MVA85A, alone and in combination. J Infect Dis. 2014 Apr 15;209(8):1259-68. doi: 10.1093/infdis/jit647. Epub 2013 Nov 23.
• Carter E, Morton B, ElSafadi D, Jambo K, Kenny-Nyazika T, Hyder-Wright A, Chiwala G, Chikaonda T, Chirwa AE, Gonzalez Sanchez J, Yip V, Biagini G, Pennington SH, Saunderson P, Farrar M, Myerscough C, Collins AM, Gordon SB, Ferreira DM. A feasibility study of controlled human infection with intradermal Bacillus Calmette-Guerin (BCG) injection: Pilot BCG controlled human infection model. Wellcome Open Res. 2024 Jun 5;8:424. doi: 10.12688/wellcomeopenres.19811.2. eCollection 2023.

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