Aerosol BCG Challenge Study in Historically BCG-vaccinated Volunteers

Inclusion Criteria: * Healthy adults aged 18-50 years * Previously vaccinated with the BCG (at least 6 months prior to enrolment, as evidenced by a visible scar or documentation in medical or occupational health records) * Resident in or near Oxford for the duration of the study period * Provide written informed consent * Willing to allow the investigators to discuss the volunteer's medical history with their General Practitioner (or review summary care record, if available) * Allow the investigator to register volunteer details with a confidential database (The Over-volunteering Protection Service) to prevent concurrent entry into clinical studies/trials * Agreement to refrain from blood donation during the course of the study * For women of child-bearing potential only, willingness to practice continuous effective contraception (see below) during the study and a negative pregnancy test on the day(s) of screening, challenge and bronchoscopy * Able and willing (in the investigator's opinion) to comply with all study requirements * No clinically relevant findings in medical history or on physical examination * Screening IGRA negative * Willing to be tested for evidence of SARS-CoV-2 infection and to allow public health notification of the results Exclusion Criteria: * Any clinically significant respiratory disease, including asthma * Current smoker (defined as any smoking including e-cigarettes in the last 3 months) * History of anaphylaxis to vaccination or any allergy likely to be exacerbated by any component of the study agent, any essential study procedure, sedative drugs, or any local or general anaesthetic agents * Clinically significant history of skin disorder, allergy, atopy, cancer (except BCC of the skin or CIS of the cervix), cardiovascular disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder, neurological illness, psychiatric disorder, drug or alcohol abuse * Any autoimmune conditions or immunodeficiency (including HIV) * Previous diagnosis or treatment for TB disease or latent TB infections * Clinical, radiological, or laboratory evidence of current active TB disease or latent TB infection * Previous receipt of any investigational TB vaccine * Positive HBsAg, HCV or HIV antibodies * Concurrent use of oral, inhaled or systemic steroid medication or use for more than 14 days within the last 6 months (steroids used as a cream or ointment are permissible), or the use of other immunosuppressive agents concurrently or for more than 14 days within the last 6 months * Administration of immunoglobulins and/or any blood products within the three months preceding the planned study challenge date * Current use of any medication or other drug taken through the nasal or inhaled route including cocaine or other recreational drugs * Any nasal, pharyngeal, or laryngeal finding which precludes bronchoscopy * Pregnancy, lactation or intention to become pregnant during study period * Previously resident for more than 12 months concurrently in a tropical climate where significant non-tuberculous mycobacterial exposure is likely * 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 * Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment, or planned use during the study period * Clinically significant abnormality on screening chest radiograph * Clinically significant abnormality of lung function testing * Any clinically significant abnormality of screening blood or urine tests * Laboratory confirmed (PCR or antibody) SARS-Cov-2 infection, evidence of viral pneumonitis on chest radiograph or a high clinical suspicion of COVID-19 disease in the 3 months preceding enrolment. * A body mass index (BMI) of \<18.5 or \>45 * 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