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The purpose of this study is to evaluate the BCG 'challenge' model a four-arm study design has been chosen. Twelve subjects will be recruited into each arm of the study. Allocation of BCG-naïve volunteers to either group A or B, and BCG-vaccinated volunteers to either group C or D, will be performed on a one-to-one alternating basis. Subjects in each group will be challenged by BCG administered intradermally. Prior to challenge, pre-existing immunity to TB will be induced by vaccination with BCG, MVA85A, and both in combination (when compared to BCG- & MVA85A-naïve individuals). BCG quantification will be assessed by analysing the tissue obtained in a punch biopsy of volunteers' skin over the site of BCG 'challenge' vaccination. Any reduction in BCG quantification between groups will then be correlated to existing (and future) laboratory assays of vaccine-induced immune responses in order to identify potential immunological correlates of protection.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group A | Experimental | BCG-naive subjects receiving intradermal "challenge" injection of BCG and challenge site punch biopsy |
|
| Group B | Experimental | BCG-naïve subjects receiving intradermal injection of MVA85A followed by intradermal "challenge" injection of BCG and challenge site punch biopsy |
|
| Group C | Experimental | BCG-experienced subjects receiving intradermal "challenge" injection of BCG and challenge site punch biopsy |
|
| Group D | Experimental | BCG-experienced subjects receiving intradermal injection of MVA85A followed by intradermal "challenge" injection of BCG and challenge site punch biopsy |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BCG: 100 microlitres ~ 2-8 x 105 pfu | Biological | BCG vaccination at day C (challenge day) then punch biopsy at day C+14 |
|
| Measure | Description | Time Frame |
|---|---|---|
| Culture and RT-PCR quantification of BCG in challenge site biopsy | 10 weeks post biopsy |
| Measure | Description | Time Frame |
|---|---|---|
| Established and exploratory markers of cell mediated immunity in blood samples and biopsied tissue | 10 weeks post biopsy |
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Inclusion Criteria:
Additional criteria to be met for subjects in group A:
Additional criteria to be met for subjects in group B:
Additional criteria to be met for subjects in group C:
Additional criteria to be met for subjects in group D:
Exclusion Criteria:
Additional exclusion criteria for subjects in group A:
Additional exclusion criteria for subjects in group B:
Additional exclusion criteria for subjects in group C:
Additional exclusion criteria for subjects in group D:
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| Name | Affiliation | Role |
|---|---|---|
| Helen McShane | University of Oxford | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Centre for Clinical Vaccinology and Tropical Medicine | Oxford | Oxon | OX3 7LJ | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31998295 | Derived | Tanner R, Satti I, Harris SA, O'Shea MK, Cizmeci D, O'Connor D, Chomka A, Matsumiya M, Wittenberg R, Minassian AM, Meyer J, Fletcher HA, McShane H. Tools for Assessing the Protective Efficacy of TB Vaccines in Humans: in vitro Mycobacterial Growth Inhibition Predicts Outcome of in vivo Mycobacterial Infection. Front Immunol. 2020 Jan 10;10:2983. doi: 10.3389/fimmu.2019.02983. eCollection 2019. | |
| 24273174 |
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| MVA85A: 1 x 108 pfu BCG: 100 microlitres ~ 2-8 x 105 pfu | Biological | MVA85A vaccination at day C-28 followed by BCG vaccination at day C (challenge day) then biopsy at day C+14 |
|
| Derived |
| 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. |
| ID | Term |
|---|---|
| D014376 | Tuberculosis |
| ID | Term |
|---|---|
| D009164 | Mycobacterium Infections |
| D000193 | Actinomycetales Infections |
| D016908 | Gram-Positive Bacterial Infections |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
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