BCG Revaccination Study in Diabetic and Non-Diabetic Adults

Prior treatment

• Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment or during the trial follow up period
• Previous diagnosis or treatment for TB disease or latent TB infections
• Previous receipt of any investigational TB vaccine or aerosolised BCG
• More than one previous BCG vaccination
• 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 a live vaccine within the preceding 28 days prior to enrolment
• Administration of any other non-live vaccine within the preceding 14 days prior to enrolment
• Previously resident for more than 12 months concurrently in the rural areas of a tropical climate where significant non-tuberculous mycobacterial exposure is likely
• Current use of any medication or other drug taken through the nasal or inhaled route including cocaine or other recreational drugs

Other illness

• 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), bleeding disorder, cardiovascular disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder (excluding T2DM in Group C only), neurological illness, psychiatric disorder, drug or alcohol abuse
• Any significant autoimmune conditions or immunodeficiency (including HIV)
• 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
• Any clinically significant respiratory disease, including asthma
• 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

Lab values

• Clinical, radiological, or laboratory evidence of current active TB disease or latent TB infection
• An HBA1c at screening of \> 48mmol/Lmol

Other

• Administration of immunoglobulins and/or any blood products within the three months preceding the planned study vaccination date
• Pregnancy, lactation or intention to become pregnant during study period
• Any other clinically significant abnormality of screening blood or urine tests
• A body mass index (BMI) of \<18.5 or \>45
  • Group A or B Specific Exclusions:
• Current smoker (defined as any smoking including e-cigarettes in the last 3 months)
• Any nasal, pharyngeal, or laryngeal finding which precludes bronchoscopy
• Clinically significant abnormality on screening chest radiograph
• Clinically significant abnormality of lung function testing

• Healthy adults aged 18-65 years
• 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 persons of child-bearing potential (POCBP) only, willingness to practice continuous effective contraception (see below) during the study and a negative pregnancy test on the day(s) of screening, vaccination and bronchoscopy
• Able and willing (in the investigator's opinion) to comply with all study requirements
• No clinically relevant findings 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 if required
• Previously vaccinated with the BCG (at least 12 months prior to enrolment, as evidenced by a visible scar or documentation in medical or occupational health records)
• Group C only - Documented diagnosis of T2DM (made at least 12 months prior to enrolment) initiated on a management plan with medication including use of metformin