Evaluating the Safety and Immunogenicity of MTBVAC

Exclusion Criteria

• •Weight less than 40 kg
• •Known significant exposure to TB or receipt of tuberculin skin test in the six months prior enrollment, as determined by the site investigator based on potential participant/parent/guardian report and available medical records. \[Note: Significant exposure is defined as close contact with a person who has active TB and has not completed TB treatment. Close contact is defined as sleeping in the same contiguous house/dwelling, and/or working or socializing in close proximity in an enclosed space frequently (eg, several times a week).\]
• •History of prior active TB disease, as determined by the site investigator based on participant/parent/guardian report and available medical, laboratory or radiographic records.
• •Evidence of active TB disease as determined by the site investigator based on participant/parent/guardian report and available medical records, results from physical examination, two-view chest X-ray, and M.tb nucleic acid testing from an expectorated sputum, including a review of any available radiography; and, for volunteers living with HIV and a CD4 count \<200 cells/mm3, a positive urine LAM test.
• •Receipt of TB preventive therapy within 28 days prior to enrollment or expected to initiate TB preventive therapy during the study as determined by the site investigator based on participant/parent/guardian report and available medical records Note: Clinical indication for receipt of TB preventive therapy will be determined by the site investigator consistent with local standard guidelines. Potential participants on TB preventive therapy during screening may be enrolled once the exclusionary timeframes indicated above have elapsed. If the screening period is exceeded while this requirement is being met, a new screening attempt should be initiated.
• •For volunteers living with HIV: current active AIDS-defining condition as determined by the site investigator based on participant/parent/guardian report and available medical records
• •Blood products received within 120 days before vaccination.
• •Investigational study products (non-vaccine) received within 28 days before vaccination.
• •Pregnant or breastfeeding.
• •Investigational TB vaccine(s) received in a prior TB vaccine trial or BCG vaccination outside infancy. For volunteers who have received control/placebo in a TB vaccine trial, the HVTN 605/A5421 PSRT will determine eligibility on a case-by-case basis.
• •Investigational non-TB vaccine(s) received within the last 1 year in a prior vaccine trial. Exceptions may be made by the HVTN 605/A5421 PSRT for vaccines that have subsequently undergone licensure by the FDA or by the national regulatory authority where the volunteer is enrolling. For volunteers who have received control/placebo in an experimental vaccine trial, the HVTN 605/A5421 PSRT will determine eligibility on a case-by-case basis. For volunteers who have received an experimental vaccine(s) greater than 1 years ago, eligibility for enrollment will be determined by the HVTN 605/A5421 PSRT on a case-by-case basis.
• •Live attenuated vaccines received within 28 days before first vaccination or scheduled within 28 days after injection (eg, measles, mumps, and rubella \[MMR\]; oral polio vaccine \[OPV\]; varicella; yellow fever; live attenuated influenza vaccine).
• •Any vaccines that are not live attenuated vaccines and were received within 14 days prior to first vaccination (eg, tetanus, pneumococcal, Hepatitis A or B).
• •Allergy treatment with antigen injections within 28 days before first vaccination or that are scheduled within 14 days after first vaccination.
• •Immunosuppressive medications received within 168 days before first vaccination (Not exclusionary: \[1\] corticosteroid nasal spray; \[2\] inhaled corticosteroids; \[3\] topical corticosteroids for mild, uncomplicated dermatologic condition; or \[4\] a single course of oral/parenteral prednisone or equivalent at doses \< 60 mg/day and length of therapy \< 11 days with completion at least 30 days prior to enrollment).
• •Serious adverse reactions to vaccines or to vaccine components including history of anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain. (Not excluded from participation: a volunteer who had a non-anaphylactic adverse reaction to pertussis vaccine as a child).
• •Immunoglobulin received within 90 days before vaccination.
• •Autoimmune disease, current or history (Not exclusionary: mild, well-controlled psoriasis)
• •Immunodeficiency (Not exclusionary: HIV).
• •Clinically significant medical condition, physical examination findings, clinically significant abnormal laboratory results, or past medical history with clinically significant implications for current health. A clinically significant condition or process includes but is not limited to:
• •1. A process that would affect the immune response,
• •2. A process that would require medication that affects the immune response,
• •3. Any contraindication to repeated injections or blood draws,
• •4. A condition that requires active medical intervention or monitoring to avert grave danger to the volunteer's health or well-being during the study period,
• •5. A condition or process for which signs or symptoms could be confused with reactions to vaccine, or
• •Any medical, psychiatric, occupational, or other condition that, in the judgment of the investigator, would interfere with, or serve as a contraindication to, protocol adherence, assessment of safety or reactogenicity, or a volunteer's ability to give informed consent, including but not limited to clinically significant substance or alcohol use disorder.
• •Psychiatric condition that precludes compliance with the protocol. Specifically excluded are persons with psychoses within the past 3 years, ongoing risk for suicide, or history of suicide attempt or gesture within the past 3 years.
• •Asthma is exclusionary if the participant has ANY of the following:
• •1\. Required either oral or parenteral corticosteroids for an exacerbation 2 or more times within the past year; OR 2. Needed emergency care, urgent care, hospitalization, or intubation for an acute asthma exacerbation within the past year (eg, would NOT exclude individuals with asthma who meet all other criteria but sought urgent/emergent care solely for asthma medication refills or coexisting conditions unrelated to asthma); OR 3. Uses a short-acting rescue inhaler more than 2 days/week for acute asthma symptoms (ie, not for preventive treatment prior to athletic activity); OR 4. Uses medium-to-high-dose inhaled corticosteroids (greater than 250 mcg fluticasone or therapeutic equivalent per day), whether in single-therapy or dual-therapy inhalers (ie, with a long-acting beta agonist \[LABA\]); OR Uses more than 1 medication for maintenance therapy daily. Inclusion of anyone on a stable dose of more than 1 medication for maintenance therapy daily for greater than 2 years requires PSRT approval.
• •Diabetes mellitus type 1 or type 2. (Not exclusionary: type 2 cases controlled with diet alone or a history of isolated gestational diabetes. For these cases, control should be confirmed with an appropriate laboratory test (eg, fasting glucose, HbA1c) based on a specimen collected during screening.)
• •Hypertension:
• •1. If a person has been found to have elevated blood pressure or hypertension during screening or previously, exclude for blood pressure that is not well controlled. Well-controlled blood pressure is defined in this protocol as consistently \< 140 mm Hg systolic and \< 90 mm Hg diastolic, with or without medication, with only isolated, brief instances of higher readings, which must be ≤ 150 mm Hg systolic and ≤ 100 mm Hg diastolic. For these volunteers, blood pressure must be \< 140 mm Hg systolic and \< 90 mm Hg diastolic at enrollment.
• •2. If a person has NOT been found to have elevated blood pressure or hypertension during screening or previously, exclude for systolic blood pressure ≥ 150 mm Hg at enrollment or diastolic blood pressure ≥ 100 mm Hg at enrollment.
• •Bleeding disorder (eg, factor deficiency, coagulopathy, or platelet disorder requiring special precautions)
• •Malignancy (Not excluded from participation: Volunteer who has had malignancy excised surgically and who, in the investigator's estimation, has a reasonable assurance of sustained cure, or who is unlikely to experience recurrence of malignancy during the period of the study).
• •Seizure disorder: History of seizure(s) within past three years. Also exclude if volunteer has used medications in order to prevent or treat seizure(s) at any time within the past 3 years.
• •Asplenia: any condition resulting in the absence of a functional spleen.
• •History of angioedema or anaphylaxis (Not exclusionary: angioedema or anaphylaxis with known trigger and no episodes within five years.)
• •History of generalized urticaria within past five years.