A feasibility study of controlled human infection with intradermal Bacillus Calmette–Guérin (BCG) injection: Pilot BCG controlled human infection model

Carter, Emma, Morton, Ben ORCID: https://orcid.org/0000-0002-6164-2854, ElSafadi, Dima, Jambo, Kondwani ORCID: https://orcid.org/0000-0002-3195-2210, Kenny-Nyazika, Tinashe, Hyder-Wright, Angela, Chiwala, Gift, Chikaonda, Tarsizio, Chirwa, Anthony, Gonzalez-Sanchez, Jonathan, Yip, Vincent, Biagini, Giancarlo ORCID: https://orcid.org/0000-0001-6356-6595, Pennington, Shaun ORCID: https://orcid.org/0000-0002-7160-6275, Saunderson, Paula, Farrar, Madlen, Myerscough, Christopher, Collins, Andrea ORCID: https://orcid.org/0000-0002-4094-1572, Gordon, Stephen ORCID: https://orcid.org/0000-0001-6576-1116 and Ferreira, Daniela ORCID: https://orcid.org/0000-0002-0594-0902 (2023) 'A feasibility study of controlled human infection with intradermal Bacillus Calmette–Guérin (BCG) injection: Pilot BCG controlled human infection model'. Wellcome Open Research, Vol 8, e424.

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Abstract

Tuberculosis (TB) caused 1.5 million deaths in 2020, making it the leading infectious killer after COVID-19. Bacille Calmette-Guerin (BCG) is the only licensed vaccine against TB but has sub-optimal efficacy against pulmonary TB and reduced effectiveness in regions close to the equator with high burden. Efforts to find novel vaccines are hampered due to the need for large-scale, prolonged, and costly clinical trials. Controlled human infection models (CHIMs) for TB may be used to accelerate vaccine development by ensuring only the most promising vaccine candidates are selected for phase 3 trials, but it is not currently possible to give participants Mycobacterium tuberculosis as a challenge agent. This study aims to replicate and refine an established BCG CHIM at the Liverpool School of Tropical Medicine. Participants will receive an intradermal injection with licensed BCG vaccine (Statens Serum Institut strain). In phase A, participants will undergo punch biopsy two weeks after administration, paired with minimally invasive methods of skin sampling (skin swab, microbiopsy, skin scrape). BCG detection by classical culture and molecular methods will be compared between these techniques and gold standard punch biopsy. Techniques meeting our pre-defined sensitivity and specificity criteria will be applied in Phase B to longitudinally assess intradermal BCG growth two, seven and fourteen days after administration. We will also measure compartmental immune responses in skin, blood and respiratory mucosa in Phase B. This feasibility study will transfer and refine an existing and safe model of BCG controlled human infection. Longitudinal BCG quantification has the potential to increase model sensitivity to detect vaccine and therapeutic responses. If successful, we aim to transfer the model to Malawi in future studies, a setting with endemic TB disease, to accelerate development of vaccines and therapeutics relevant for underserved populations who stand to benefit the most. Registration: ISRCTN: ISRCTN94098600 and ClinicalTrials.gov: NCT0582059

Item Type:	Article
Subjects:	QW Microbiology and Immunology > Immune Responses > QW 700 Infection. Mechanisms of infection and resistance. QW Microbiology and Immunology > Immunotherapy and Hypersensitivity > QW 806 Vaccination WF Respiratory System > Tuberculosis > WF 200 Tuberculosis (General)
Faculty: Department:	Clinical Sciences & International Health > Clinical Sciences Department Clinical Sciences & International Health > Malawi-Liverpool-Wellcome Programme (MLW)
Digital Object Identifer (DOI):	https://doi.org/10.12688/wellcomeopenres.19811.1
SWORD Depositor:	JISC Pubrouter
Depositing User:	JISC Pubrouter
Date Deposited:	13 Oct 2023 10:15
Last Modified:	13 Oct 2023 10:15
URI:	https://archive.lstmed.ac.uk/id/eprint/23314

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