Investigating Immune Responses to Aerosol BCG Challenge in Healthy UK Adults

Inclusion Criteria: * Healthy adult aged 18-50 years * Resident in or near Oxford for the duration of the study period * Screening IGRA negative * No relevant findings in medical history or on physical examination * Allow the Investigators to discuss the individual's medical history with their GP * Use effective contraception (see below) for the duration of the study period (people of child bearing potential only) * Refrain from blood donation during the study * Give written informed consent * Allow the Investigator to register volunteer details with a confidential database (The Over-volunteering Protection Service) to prevent concurrent entry into clinical studies/trials * Willing to be tested for evidence of SARS-CoV-2 infection, if indicated and to allow public health notification of results if required. * Able and willing (in the Investigator's opinion) to comply with all the study requirements * For Group 8 only- previously vaccinated with BCG (at least 12 months prior to enrolment, as evidenced by a visible scar or documentation in medical or occupational health records) Exclusion Criteria: * Previously resident for more than 12 months concurrently in a rural area of a tropical climate where significant non-tuberculous mycobacterial exposure is likely * Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment, or planned use during the study period * Prior vaccination with BCG (G1-7 only) or any other candidate TB vaccine (all groups). * Administration of immunoglobulins and/or any blood products within the three months preceding the planned study challenge date * Clinically significant history of skin disorder, allergy, atopy, immunodeficiency (including HIV), cancer (except BCC or CIS), cardiovascular disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder, neurological illness, psychiatric disorder, drug or alcohol abuse * Concurrent oral, inhaled or systemic steroid medication or the concurrent use of other immunosuppressive agents * Shares a household with someone with clinically significant immunodeficiency (either from infection or medication) who is deemed to be at risk of developing disseminated BCG infection if exposed to BCG * History of anaphylaxis to vaccination or any allergy likely to be exacerbated by any component of the study agent, essential study procedures, sedative drugs, or any local or general anaesthetic agents * Pregnancy, lactation or intention to become pregnant during study period * Any clinically significant respiratory disease, including asthma * Current smoker (defined as any smoking including e-cigarettes in the last 3 months) * Clinically significant abnormality on screening chest radiograph * Clinically significant abnormality of pulmonary function * Any nasal, pharyngeal, or laryngeal finding which precludes bronchoscopy * Current use of any medication taken through the nasal or inhaled route including cocaine or other recreational drugs * Clinical, radiological, or laboratory evidence of current active TB disease * Past treatment for TB disease * Any clinically significant abnormality of screening blood or urine tests * Positive HBsAg, HCV or HIV antibodies * Any other significant disease, disorder, or finding, which, in the opinion of the Investigator, may either put the volunteer at risk, affect the volunteer's ability to participate in the study or impair interpretation of the study data People of Child Bearing Potential (POCBP) are required to use an effective form of contraception during the course of the study. Acceptable forms of contraception for POCBP volunteers include: * Established use of oral, injected on implanted hormonal methods of contraception * Placement of an intrauterine device (IUD) or intrauterine system (IUS) * Permanent sterilisation or bilateral tubal occlusion * Barrier methods of contraception (condom; or occlusive cap with spermicide) * Male sterilisation, if the vasectomised partner is the sole partner for the subject * True abstinence, when this is in line with the preferred and usual lifestyle of the subject (periodic abstinence and withdrawal are not acceptable methods of contraception) * Exclusive same sex intercourse