Safety, Immunogenicity, and Efficacy of Therapeutic Mycobacterium Bovis BCG (BOOST)

Inclusion Criteria In order to be eligible to participate in this study, an individual must meet all of the following criteria: 1. Male or female aged ≥18 years 2. Mycobacterium avium complex lung disease as evidenced by diagnosis or treatment for MAC lung disease by pulmonologist or infectious disease physician in the medical record. The following data will be extracted from the medical record: 1. History of at least 2 MAC positive respiratory cultures, one of which is within 1 year of enrollment. In the event a MAC positive culture is from bronchial lavage or biopsy, one culture rather than 2 will meet criteria. 2. Respiratory and/or constitutional symptoms consistent with MAC lung disease 3. Nodular or cavitary opacities on chest radiograph or bronchiectasis with multiple small nodules on high-resolution computed tomography 3. Provision of signed and dated informed consent form 4. Stated willingness to comply with all study procedures 5. Women of childbearing potential (WOCBP) (i.e., fertile following menarche and until becoming postmenopausal unless permanently sterile) agree to practice a highly effective method of birth control from Day 0 to at least 90 days after study intervention. Some examples of acceptable birth controls are: 1. True abstinence (refraining from heterosexual intercourse during the entire study), 2. Copper intrauterine device (IUD), 3. Hormonal methods (levonorgestrel-releasing intrauterine system, progestogen implant, combined oral contraceptive pill \[combined with barrier method\]), exclusive homosexual relationship) sole male partner who has undergone surgical sterilization Exclusion Criteria Selection of study participants will be equitable, but an individual who meets any of the following criteria will be excluded from participation in this study: 1. Currently receiving antibiotics prescribed for their MAC lung disease 2. Having received any antibacterial antibiotics within the past 14 days prior to study vaccination, day 0 3. Known allergy, intolerance or other contraindication to isoniazid or rifampin or ethambutol 4. Expectation of starting anti-MAC lung disease antibiotics in the next 2 months per patient or their physician 5. Persons with congenital or acquired immune deficiencies (e.g., HIV infection; leukemia, lymphoma, or cancer therapy within the past 2 years; immunosuppressive therapy such as anti B cell depleting therapies, corticosteroids (\>20 mg/day for \> 14 days), dupilumab, elivaldogene, etrasimod, cytotoxic chemotherapy, miscellaneous oncologic agents, therapeutic immunosuppressant agents, methotrexate, teplizumab, tezepelumab, tildrakizumab, tralokinumab, ustekinumab). Persons with lung and other solid organ transplants/hematologic stem cell transplants who may be contraindicated to receive a live vaccine. Point of care HIV testing must be negative at baseline. 6. Prior BCG Vaccination. If unknown Bcgatlas.org shall be consulted for local vaccination administration policies. 7. Known pregnancy at the time of screening or breastfeeding at the time of enrollment (pregnancy test negative at baseline if applicable) 8. Cystic fibrosis 9. Active tuberculosis: Active tuberculosis (respiratory AFB culture growing Mycobacterium tuberculosis complex within the past 4 months). 10. Known exposure to a case of active pulmonary tuberculosis within 10 weeks of enrollment 11. Known prior hypersensitivity reaction to BCG or any component of the BCG vaccine 12. Received live injectable vaccine within 28 days of day 0 study vaccination 13. Any condition in the opinion of the investigator that may confound the study endpoints Note that colonization or co-infection with other nontuberculous mycobacteria is not exclusionary, as MAC will be the endpoint.