Study to Assess Efficacy and Safety of M72/AS01E-4 Mycobacterium Tuberculosis (Mtb) Vaccine in Adolescents and Adults

Inclusion criteria:

• Capable of giving informed consent or informed assent (as appropriate). Forparticipants below the age of consent, the participant's parent, or legallyauthorized representative (LAR) will be required to sign a statement of informedconsent, in addition to the minor's signed statement of assent.

• In the opinion of the investigator, can and will comply with the requirements of theprotocol (e.g., completion of diary cards as applicable, and return for follow-upvisits).

• Agree to actively stay in contact with the trial site for the duration of the trialfor the participants own safety.

• Agree to provide updated contact information as necessary, and have no current plansto relocate from the trial area for the duration of the trial.

• Healthy, or with preexisting stable disease, as established by medical history andphysical examination and as determined by the investigator.

• Negative sputum Xpert Ultra or similar assay result at screening.

• Both males and females are included. Females are included with restrictions. Femalesmust either be of non-childbearing potential, defined as pre-menarche, have ahistory of either current tubal ligation, hysterectomy, or ovariectomy, orpost-menopause, or, if she is of childbearing potential, she has practicedabstinence from penile-vaginal intercourse or adequate contraception for 28 daysprior to vaccination, has a negative pregnancy test on the day of screening and theday of first vaccination, and agrees to continue abstinence or adequatecontraception until 2 months after the second dose of trial intervention.

• HIV-negative test result at screening (IGRA-Positive Cohort and IGRA-Negative Cohortonly).

• HIV Cohort only: Participants with documented HIV infection who fulfill all of thefollowing criteria:

1. Have reactive anti-HIV antibody at screening.

2. Have been on antiretroviral therapy (ART) for at least 3 consecutive months atscreening and agree to remain on ART throughout the trial.

3. Have documented HIV Ribonucleic acid (RNA) <200 copies per milliliter (/mL) atscreening.

4. Have Cluster of differentiation (CD)4+ cell count ≥200 cells/microliter (μL) atscreening.

5. Have had Tuberculosis preventive therapy (TPT) in the past and are notreceiving TPT at the time of screening, according to the judgment of theinvestigators.

6. Have an IGRA-positive or negative result at screening.

Exclusion criteria:

• Current TB, or history of TB or treatment for TB disease.

• Clinical suspicion of pulmonary TB at screening, defined as a participant presentingwith one or more of the following signs or symptoms: unexplained cough, unexplainedfever, night sweats, unintentional weight loss, hemoptysis, pleuritic chest pain.

• Any current medical, psychiatric, occupational, or substance abuse problems that, inthe opinion of the investigator, will make it unlikely that the participant willcomply with the protocol, or that will interfere with the assessments or the safetyof the participant.

• Any confirmed or suspected immunosuppressive or immunodeficient condition resultingfrom disease (e.g., invasive, or malignant cancers), other than HIV infection in theHIV Cohort.

• Known bleeding disorder that is considered a contraindication to intramuscularinjection or phlebotomy.

• Any cytotoxic drugs or administration of medications known to have a major impact onthe immune system, as determined by the investigator, within 90 days prior to Day 1.These include immune globulin, blood, or blood products, potent immunosuppressantsand immunomodulators, and systemic corticosteroids (exceeding 20 mg/day prednisoneequivalent). Inhaled, topical, and intra-articular corticosteroids are allowed.

• Planned receipt of blood, or blood products during the trial period.

• Receipt or planned receipt of any vaccine in the period starting 28 days before, andending 28 days after, each dose of the trial vaccine.

• History of previous administration of an experimental Mtb vaccine includingM72/AS01E in a previous trial.

• History of allergy or hypersensitivity to the trial intervention, excipients, orrelated Substances.

• An indeterminate IGRA test result at screening

• Female participants with any one of the following conditions: currently pregnant orlactating; having positive serum pregnancy test during the screening window,positive urine pregnancy test on Day 1, planning a pregnancy within 2 months aftercompletion of the vaccination series.

• Only in the HIV Cohort: Safety laboratory values at screening that are of concern,based on investigator's judgment. Note that preexisting stable chronic disease willnot necessarily lead to exclusion, especially if laboratory values are graded asmild.

• Participation in an interventional clinical trial in which the participant has beenor will be exposed to an investigational product (pharmaceutical product or device),within 28 days prior to signing consent or assent, or during the trial period.

• Individuals who are acting as personnel for this trial, or who have immediate familymembers (brother, sister, child, parent, or the spouse/partner) who are acting aspersonnel for this trial.

• Child in Care, defined as a child who is under the care (control or protection) ofan agency, organization, institution or entity by the courts, the government body,acting in accordance with powers conferred in them by law or regulations. Thedefinition of a child in care can include a child who is cared for by foster parentsor living in a care home or institution, provided that the arrangements fall withinthe definition above. The definition of a child in care does not include a child whois adopted or has an appointed LAR.

• Participants who had a Tuberculin Skin Test (TST) within 6 months prior to Day 1.