Biological Samples Obtained by Leukapheresis Induced by Two BCG Vaccinations in BCG-naïve Healthy Adults in the US

This is an open-label protocol in up to 15 healthy adults who are BCG-naïve. All participants will receive a total of two doses of BCG, by intradermal injection, approximately 6 months apart. Participants will be followed by a combination of visits and telephone contacts through Study Day 264. Participants will undergo TST testing 3 months after the second BCG vaccination and QuantiFERON TB Gold in-Tube (QTBGT), or the equivalent, if necessary. Two BCG vaccinations given 6 months apart were chosen for this study to give optimal T cell and antibody responses for future study. Leukapheresis will be conducted prior to the first BCG vaccination and at 56 days after the second BCG vaccination (Hoft, 2002; Brown, 2003; de Valliere, 2005). The final leukapheresis timing was selected based on results from functional biological assays, which suggest analysis of samples at this time point may provide insight into the protective immune responses elicited by BCG, and on results of prior clinical trials describing the peak immune responses to BCG (Hoft, 2002; Brown, 2003; de Valliere, 2005). The study will be conducted at a single site in the US (Saint Louis University [SLU]).

Inclusion criteria

• Has completed the written informed consent process.
• Is age ≥18 years and ≤55 years on Study Day 0.
• Agrees to stay in contact with the study site for the duration of the study, provide updated contact information as necessary, and has no current plans to move from the study area for the duration of the study.
• Agrees to avoid elective surgery during the study.
• Willingness to receive HIV test results.
• For female participants: agrees to avoid pregnancy from 21 days prior to Study Day 0 and for the full duration of the study. Women physically capable of pregnancy (not sterilized and still menstruating or within 1 year of the last menses if menopausal) in sexual relationships with men must use an acceptable method of avoiding pregnancy during this period. Acceptable methods of avoiding pregnancy include a sterile sexual partner, sexual abstinence (not engaging in sexual intercourse), hormonal contraceptives (oral, injection, transdermal patch, or implant), vaginal ring, intrauterine device (IUD), or the combination of a condom or diaphragm with spermicide.
• Has general good health, confirmed by medical history and physical examination.
• Has not received vaccination or immunotherapy with a BCG product at any time prior to Study Day 0.
• Body weight of > 110 pounds
• Absence of previous risk factors for HIV infection including:

• History of IV drug abuse
• History of unprotected intercourse with known HIV infected individual
• Men having sex with men

Exclusion criteria

Participants must have none of the following at the time of study entry:

• Acute illness on Study Day 0.
• HIV-1/2 positive
• Oral temperature ≥37.5°C on Study Day 0.
• Abnormal laboratory values per local laboratory parameters from most recent blood collection prior to Study Day 0 as follows:

• hemoglobin, hematocrit, absolute neutrophil count, or absolute lymphocyte count below lower limit of normal (LLN)
• white blood cell count above upper limit of normal (ULN) or below LLN (i.e., must be within normal limits)
• ALT, AST, GGT, total bilirubin, alkaline phosphatase (ALP), blood urea nitrogen (BUN), creatinine >1.25 times institutional upper limit of normal
• Calcium not within institutional normal limits
• Fibrinogen level <100 mg/dL.
• Evidence of significant active infection.
• Evidence of central nervous system tuberculosis or pleural tuberculosis.
• Positive QuantiFERON TB Gold in-Tube (or equivalent).
• History of treatment for active or latent tuberculosis infection.
• History or evidence of active tuberculosis.
• Shared a residence within the last year with an individual on anti-tuberculosis treatment or with culture or smear positive tuberculosis.
• History of occupational exposure to an individual with active tuberculosis in a health care setting.
• History of autoimmune disease or immunosuppression.
• Used immunosuppressive medication within 42 days before Study Day 0 (inhaled and topical corticosteroids are permitted).
• Received immunoglobulin or blood products within 42 days before Study Day 0.
• Received any investigational drug or investigational vaccine within 182 days before Study Day 0, or planned participation in any other interventional study during the study period.
• Received investigational TB vaccine at any time.
• Planned administration/administration of a licensed vaccine in the period starting 28 days before and ending 56 days after the last BCG vaccination in this study.
• Current chronic drug therapy including hormone replacement such as thyroxin, insulin, etc. (estrogen and progesterone replacement and contraceptives are acceptable).
• History or laboratory evidence of any past, present, or future possible immunodeficiency state including but not limited to any laboratory indication of HIV-1 infection.
• Any contraindications for BCG administration as described in the BCG package insert (Appendix B).
• Previous medical history that may compromise the safety of the participant in the study, including but not limited to: severe impairment of pulmonary function from tuberculosis infection or other pulmonary disease; chronic illness with signs of cardiac or renal failure; suspected progressive neurological disease; or uncontrolled epilepsy.
• Evidence of a new acute illness that may compromise the safety of the participant in the study.
• History or evidence of chronic hepatitis.
• History of alcohol or drug abuse within the past 2 years.
• History of keloid formation.
• History or evidence on physical examination of any systemic disease or any acute or chronic illness that, in the opinion of the investigator, may interfere with the evaluation of the safety or immunogenicity of BCG, including axillary lymphadenopathy.
• All female participants: currently pregnant or lactating/nursing; or positive urine pregnancy test during screening, on the day of BCG vaccination.
• History of being deferred as a blood donor because of problems associated with tolerating the procedure.
• Having donated > 120 mL of blood within the last 8 weeks.
• Any current medical, psychiatric, occupational, or substance abuse problems that, in the opinion of the investigator, will make it unlikely that the participant will comply with the protocol.
• In the opinion of the investigator and the infusion center team, condition of the participant's veins is not suitable for leukapheresis procedure.