Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase I, Open Label Trial to Evaluate the Safety and Immunogenicity of AERAS-402 Followed by MVA85A in BCG Vaccinated Adults (TB032)
Brief Summary: This trial will investigate the administration of two new tuberculosis vaccines, called AERAS-402 and MVA85A. The purpose of this trial is to assess what happens when both of these vaccines are given one after the other. The trial will assess the safety of both vaccines and also their ability to stimulate an immune response within the body. It is hoped that when these two vaccines are given in sequence, the combined immune response is even better than when each vaccine is used individually.


Options:
A: 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
B: 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
C: Inclusion Criteria:

Subjects must meet all of the following criteria to enter the trial:

* Healthy adult aged 18-55 years
* Resident in or near Oxford (for CCVTM) or Birmingham (for WTCRF; and able to travel to Oxford for vaccinations) for the duration of the trial period
* No relevant findings in medical history or on physical examination
* Confirmation of prior vaccination with BCG not less than 6 months prior to projected trial vaccination date (by visible BCG scar on examination or written documentation)
* Allow the Investigators to discuss the individual's medical history with their GP
* Use effective contraception for the duration of the trial period (females only)
* Refrain from blood donation during the trial
* Give written informed consent
* Allow the Investigator to register subject details with a confidential database to prevent concurrent entry into clinical trials
* Agrees to avoid elective surgery for the duration of the trial
* Has a body mass index (BMI) between 18 and 33 (weight/height2) by nomogram
* Able and willing (in the Investigator's opinion) to comply with all the trial requirements

Exclusion Criteria:

Subjects must meet none of the following criteria to enter the trial:

* Laboratory evidence at screening of latent M. tb infection as indicated by a positive ELISPOT response to ESAT6 or CFP10 antigens
* Clinical, radiological, or laboratory evidence of current active TB disease
* Shared a residence within one year prior to day 0 with an individual on anti-tuberculosis treatment or with culture- or smear-positive pulmonary tuberculosis
* Previous treatment for active or latent tuberculosis infection
* Received a TST within 90 days prior to day 0
* Received a systemic antibiotic within 14 days prior to day 0
* Inability to discontinue daily medications other than the following during the trial: oral contraceptives, vitamins, nonprescription nutritional supplements, aspirin, antihistamines, antihypertensives, antidepressants, inhaled steroids, bronchodilators, and any other stable, regular medication not deemed to have an impact on safety or immunogenicity.
* Previous vaccination with candidate vaccine MVA85A or candidate vaccine FP85A or any other recombinant MVA or adenoviral vaccine; AERAS-402; or any other investigational M. tb vaccine
* Clinically significant history of skin disorder, allergy, immunodeficiency (including HIV), autoimmune disease, cancer (except BCC or CIS), cardiovascular disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder, neurological illness, psychiatric disorder, drug or alcohol abuse
* History of serious psychiatric condition
* Concurrent oral or systemic steroid medication or the concurrent use of other immunosuppressive agents
* History of anaphylaxis to vaccination or any allergy likely to be exacerbated by any component of the trial vaccine, including eggs
* Any abnormality of screening blood or urine tests that is deemed to be clinically significant or that may compromise the safety of the subject in the triala
* Positive HBsAg, HCV or HIV antibodies
* Female currently lactating, confirmed pregnancy or intention to become pregnant during trial period
* Use of an investigational medicinal product or non-registered drug, live vaccine, or medical device other than the trial vaccine for 30 days prior to dosing with the trial vaccine, or planned use during the trial period
* Administration of immunoglobulins and/or any blood products within the three months preceding the planned trial vaccination date
* Any other significant disease, disorder, or finding, which, in the opinion of the Investigator, may either put the subject at risk or may influence the result of the trial or may affect the subject's ability to participate in the trial
D: 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. Previous residence in a TB endemic area.
* 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
* Previous MVA immunisations

Answer: C