Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase II, Proof of Concept, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Protective Efficacy Against TB Disease, Safety, and Immunogenicity of MVA85A/AERAS-485 in Healthy, HIV-infected Adults
Brief Summary: This is a phase II, proof of concept, randomized, double-blind, placebo-controlled study to evaluate the protective efficacy against TB disease, safety, and immunogenicity of MVA85A/AERAS-485 in healthy, HIV-infected adults.

This study consists of 650 adults subjects (ages 18-50 years of age inclusive) who will receive study vaccine or placebo at Study Day 0 and again 6-9 months later. Samples for real-time evaluation of immunogenicity were to be collected from 70 subjects (immunogenicity analysis set).


Options:
A: Inclusion Criteria:

* Healthy adult aged 18-55 years.
* Normal medical history and physical examination.
* Normal urine dipstick, blood count, liver enzymes, and creatinine.

Exclusion Criteria:

* Exposure to TB at any point. A positive ESAT6/CFP10 Elispot response (defined as greater than 5 spots/well above background and at least double the background response).
* Clinically significant history of skin disorder (eczema, psoriasis, etc.), allergy, immunodeficiency, cardiovascular disease, respiratory disease, endocrine disorder, liver disease, renal disease, gastrointestinal disease, neurological illness, psychiatric disorder, drug or alcohol abuse.
* Oral or systemic steroid medication or the use of immunosuppressive agents.
* Positive HIV antibody test, HCV antibody test or positive HBV serology except post-vaccination.
* Heaf test greater than Grade II
* Confirmed pregnancy
B: Inclusion Criteria:

* Healthy adults aged 18 to 50 years
* Resident in or near Dakar for the duration of the study
* Willingness to allow the investigators to discuss the volunteer's medical history with the volunteer's HIV lead physician
* Willing to use effective contraception throughout duration of study (if female)
* HIV antibody positive; diagnosed at least 6 months previously
* CD4 count \>300
* Arm 1: HIV viral load not \>100,000 copies per millilitre
* Arm 2: Undetectable HIV viral load
* Written informed consent

Exclusion Criteria:

* Any clinically significant abnormal finding on screening biochemistry or haematology blood tests or on urinalysis
* Group 1 only: Any ARV therapy within the past 6 months
* Previous history of TB disease and/or treatment
* Any AIDS defining illness
* Group 1: CD4 count nadir \<300
* Group 2: CD4 count nadir \<100
* CXR showing TB or evidence of other active infection
* Prior receipt of a recombinant MVA or Fowlpox vaccine
* Use of any investigational or non-registered drug, live vaccine or medical device other than the study vaccine within 30 days preceding dosing of study vaccine, or planned use during the study period
* Administration of chronic (defined as more than 14 days) immunosuppressive drugs or other immune modifying drugs within six months of vaccination. (For corticosteroids, this will mean prednisolone, or equivalent, ≥ 0.5 mg/kg/day. Inhaled and topical steroids are allowed.)
* History of allergic disease or reactions likely to be exacerbated by any component of the vaccine, e.g. egg products
* Presence of any underlying disease that compromises the diagnosis and evaluation of response to the vaccine (including evidence of cardiovascular disease, history of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ), history of insulin requiring diabetes mellitus, any ongoing chronic illness requiring ongoing specialist supervision (e.g., gastrointestinal), and chronic or active neurological disease)
* History of \> 2 hospitalisations for invasive bacterial infections (pneumonia, meningitis)
* Suspected or known current drug and/or alcohol abuse
* Seropositive for hepatitis B surface antigen (HBsAg) and/ or hepatitis C (antibodies to HCV)
* Evidence of serious psychiatric condition
* Any other on-going chronic illness requiring hospital specialist supervision
* Any confirmed or suspected immunosuppressive or immunodeficient condition, other than HIV infection, such as asplenia
* Evidence of hepatomegaly
* Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate
* Pregnant/lactating female and any female who is willing or intends to become pregnant during the study
* Any history of anaphylaxis in reaction to vaccination
* PI assessment of lack of willingness to participate and comply with all requirements of the protocol, or identification of any factor felt to significantly increase the participant's risk of suffering an adverse outcome
C: Inclusion Criteria:

* Healthy adult aged 18 to 50 years
* Resident in or near Oxford for the duration of the vaccination study
* Immunization with BCG greater than 12 months prior to enrolment in the study
* Able and willing (in the Investigators' opinions) to comply with all study requirements
* Willing to allow the investigators to discuss the volunteer's medical history with their General Practitioner
* Agreement to practice barrier contraception from the start of the study until 3 months after the final vaccination
* For females, a negative pregnancy test on the day of vaccination and agreement to practice effective contraception for the entire duration of the study
* Agreement to refrain from blood donation during the course of the study
* Written informed consent

Exclusion Criteria:

* Participation in another research study involving an investigational product in the 30 days preceding enrolment, or planned use during the study period
* Prior receipt of a recombinant MVA or fowlpox vaccine
* Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate
* Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (inhaled and topical steroids are allowed)
* History of allergic disease or reactions likely to be exacerbated by any component of the vaccine, e.g. egg products
* Any history of anaphylaxis in reaction to vaccination
* Close contact with fowl during the study period (e.g. chicken farming)
* History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ)
* History of serious psychiatric condition
* Any other chronic illness requiring hospital specialist supervision
* Suspected or known current injecting drug or alcohol abuse (as defined by an alcohol intake of greater than 42 units every week)
* Seropositive for hepatitis B surface antigen (HBsAg)
* Seropositive for hepatitis C virus (antibodies to HCV)
* For females, pregnancy, lactation or willingness/intention to become pregnant during the study
* Any other significant disease, disorder or finding, which, in the opinion of the Investigators, may either put the volunteer at risk because of participation in the study, or may influence the result of the study, or the volunteer's ability to participate in the study.
* Mantoux skin test equal to or greater than 15 millimetres
* Screening Elispot positive (greater than 17 sfc/million PBMC) in any ESAT6 peptide or CFP10 peptide pool
* Any clinically significant abnormal finding on screening biochemistry or haematology blood tests or urinalysis
D: Inclusion Criteria:

* Has completed the written informed consent process prior to undergoing any screening evaluations.
* Either males or females aged 18-50 years (inclusive) on Study Day 0
* In general good health, confirmed by medical history and physical examination
* Has ability to complete follow-up period as required by the protocol
* Has laboratory evidence of human immunodeficiency virus (HIV) infection, defined as a positive HIV-1 ELISA test plus a positive confirmatory test (e.g., a second HIV-1 ELISA, polymerase chain reaction (PCR), or rapid ELISA) diagnosed prior to randomization
* Is willing to allow the investigators to discuss the subject's medical history with the subject's HIV physician
* Has 2 CD4+ lymphocyte count test results \>350 cells/mm3, performed at least 4 weeks apart, one performed within 6 months prior to randomization and one within 30 days prior to randomization
* Has either: a) a negative QuantiFERON-TB Gold In-Tube test result and tuberculin purified protein derivative (PPD) skin test ≤5 mm induration within 30 days prior to randomization or; b) a positive QuantiFERON-TB Gold In-Tube test result and/or tuberculin PPD skin test \>5 mm and has completed 6 months of isoniazid preventive therapy prior to randomization or; c) a positive QuantiFERON-TB Gold In-Tube test result and/or tuberculin PPD skin test \>5 mm and has completed treatment for TB disease within 3 year prior to randomization
* Females: Ability to avoid pregnancy during the trial. 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 avoid pregnancy by using an acceptable method of avoiding pregnancy from 28 days prior to administration of the study vaccine through the end of the study. 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 use of a condom or a diaphragm combined with spermicide.
* Has completed the written informed consent process for simultaneous enrollment in Aeras Vaccine Development Registry protocol

Exclusion Criteria:

* Acute illness
* Fever (temperature \> 37.5°C)
* Significant symptomatic infection
* Any evidence of active tuberculosis (TB) disease, as determined by any clinical, radiological, or microbiology measurements.
* Any AIDS defining illness by WHO criteria
* Has received antiretroviral therapy (ART) in the two months prior to study entry (women who have received ART as part of the Prevention of Mother-to-Child Transmission \[PMTCT\] program and completed this more than 2 months prior to randomization ARE eligible)
* Use of any investigational or non-registered drug, vaccine or medical device other than the study vaccine within 182 days preceding dosing of study vaccine, or planned use during the study period
* Previous receipt of a recombinant modified vaccinia Ankara (MVA) or fusion protein (FP) vector at any time.
* Is enrolled in any other clinical product trial
* Administration of methotrexate, azathioprine, cyclophosphamide, oral corticosteroids (for corticosteroids, this will mean prednisolone, or equivalent, ≥0.5 mg/kg/day; inhaled and topical steroids are allowed) and other immunosuppressive therapies, or blood products or blood derivatives within the six months prior to randomization
* History of allergic disease or reactions likely to be exacerbated by any component of the vaccine, e.g. egg products
* Presence of any history of cancer \[except basal cell carcinoma of the skin and cervical carcinoma in situ\], or renal failure
* Evidence of severe depression, schizophrenia or mania
* Pregnant females and females who are breast-feeding
* Any history of anaphylaxis in reaction to vaccination
* Principal investigator assessment of lack of willingness to participate and comply with the protocol, or increase in the participant's risk of adverse outcome

Answer: D