This is a Phase I, double-blind, randomized, placebo-controlled safety and immunogenicity study in adults who have recently been successfully treated for drug-susceptible pulmonary Tuberculosis (TB). The safety and immunogenicity profile of escalating doses of AERAS-456 in HIV-negative subjects recently treated for drug-susceptible pulmonary TB will be investigated. The study will be conducted at three sites in South Africa.

This study will be the first evaluation of AERAS-456 in subjects who have completed a full course of treatment prescribed for pulmonary TB. Subjects will begin screening for study participation when they have completed 4 calendar months of TB treatment. Subjects meeting the inclusion/exclusion criteria will be randomized within a study group in a 3:1 ratio (N=18 AERAS-456; N=6 placebo) to receive two 0.5 mL intramuscular injections of AERAS-456 or placebo eight weeks apart, on Study Day 0 and Study Day 56.

Inclusion Criteria:

1. Is HIV-negative.
2. Is male or female aged 18 through 60 years on Study Day 0.
3. Has completed the written informed consent process.
4. Has a diagnosis of confirmed pulmonary tuberculosis and is on standard TB treatment.
5. Is confirmed to be Mtb negative by either 2 GeneXpert tests or 2 cultures from sputum samples taken on 2 different days at least 1 week apart, the first after at least 4 calendar months of TB treatment and the second day not later than after 5 calendar months (with a window of plus 1 week) of treatment.
6. Agrees to complete the prescribed course of TB treatment (completion of TB treatment can occur after vaccination on Study Day 0; subject must have completed at least 5 calendar months of TB treatment on Study Day 0; if TB treatment is completed before randomization/vaccination then the time from completion of TB treatment to randomization/vaccination should not exceed 28 days).
7. For female subjects: agrees to avoid pregnancy between screening and up until two months after last vaccination. 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 from 28 days prior to administration of study vaccine up until two months after the last vaccination. 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, or intrauterine device (IUD).
8. Agrees to stay in contact with the study site for the full duration of the study, providing updated contact information as necessary, and has no current plans to move from the study area during the duration of the study.

Exclusion Criteria:

1. Evidence of a new acute illness that may compromise the safety of the subject in the study on Study Day 0.
2. History of TB prior to current episode.
3. TB meningitis or other forms of severe TB with high risk of a poor outcome.
4. Previous medical history that may compromise the safety of the subject 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.
5. Evidence of any systemic disease or any acute or chronic illness that may interfere with the evaluation of the safety of the vaccine.
6. History or laboratory evidence of any possible immunodeficiency state.
7. History of allergic disease or reactions likely to be exacerbated by any component of the study vaccine.
8. Received any non-BCG TB vaccine previously.
9. For female subjects: Currently pregnant, lactating/nursing, or a positive urine HCG.
10. Severe anemia, defined as hemoglobin less than 10 g/dL or a hematocrit less than 30 percent based on screening hematology obtained within 7 days before randomization on Study Day 0.
11. History of autoimmune disease or immunosuppression.
12. Used immunosuppressive medication within 42 days before Study Day 0 (inhaled and topical corticosteroids are permitted).
13. Received immunoglobulin or blood products within 42 days before Study Day 0.
14. Received any investigational drug therapy or investigational vaccine within 6 months before Study Day 0, or planned participation in any other investigational study during the study period.
15. Received any licensed vaccine within 28 days before Study Day 0, or receipt of any vaccine or immunomodulating agent through Study Day 63.
16. Is, in the judgment of the principal investigator, not suitable to participate in this clinical study.

Unsolicited AEs: for 28 days after each vaccination. Solicited AEs: for 7 days after each vaccination (with diary cards). SAEs: for entire study period (i.e., Study Days 0 to 420). Adverse events of special interest: for entire study period (i.e., Study Days 0 to 420).