Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase I Study Evaluating the Safety and Immunogenicity of a New TB Vaccine, MVA85A, in Healthy Volunteers Who Are Latently Infected With Mycobacterium Tuberculosis.
Brief Summary: This study is designed to evaluate the safety of MVA85A in healthy volunteers in the UK who are latently infected with M.tb. A single vaccination with MVA85A, when administeredat a dose of 5 x 107pfu intradermally, is safe in both mycobacterially naïve individuals and those previously vaccinated with BCG. We will use the same vaccination regime in this study. Subjects will be defined as being latently infected if they have a positive elispot response to ESAT6 or CFP10. Subjects will be identified from TB contact clinics.


Options:
A: Inclusion Criteria

* Healthy adults aged 18 to 50 years
* Resident in or near Oxford for the duration of the vaccination study
* Willingness to allow the investigators to discuss the volunteer's medical history with the volunteer's GP
* Screening Elispot positive (more than 50 spots/million PBMC) for at least any 1 of the 3 ESAT6 peptide pools or any one of the 3 CFP10 pools ; and screening Elispot positive for PPD.
* Heaf test grade II-IV or positive Mantoux test.
* CXR normal; or abnormal but not clinically significant CXR findings with no evidence of past/present TB infection or disease on the CXR.
* For females only, willingness to practice continuous effective contraception during the study and a negative pregnancy test on the day of vaccination
* Agreement to refrain from blood donation during the course of the study
* Written informed consent
* Willingness to undergo an HIV

Exclusion Criteria

* Any deviation from the normal range in biochemistry or haematology blood tests or in urine analysis
* Heaf grade IV
* 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, ε 0.5 mg/kg/day. Inhaled and topical steroids are allowed.)
* Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection and asplenia
* History of allergic disease or reactions likely to be exacerbated by any component of the vaccine, e.g. egg products
* 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
* Chronic or active neurological disease requiring ongoing specialist supervision
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:

* Healthy adult aged 18-55 years
* Resident in or near Oxford for the duration of the study period
* No relevant findings in medical history or on physical examination
* Willingness to allow the Investigators to discuss the individual's medical history with their GP
* Willingness to use effective contraception for the duration of the study period (females only)
* Agreement to refrain from blood donation during the course of the study
* Willingness to give written informed consent
* Agreement to allow the Investigator to register volunteer details with a confidential database to prevent concurrent entry into clinical trials
* Able and willing (in the Investigator's opinion) to comply with all the study requirements

Additional criteria to be met for subjects in group A:

* None

Additional criteria to be met for subjects in group B:

* Willingness to use continuous effective barrier contraception for three months after receiving
* MVA85A vaccination (males and females)

Additional criteria to be met for subjects in group C:

* Confirmation of prior vaccination with BCG not less than three months prior to projected study enrolment date (by visible BCG scar on examination or written documentation)

Additional criteria to be met for subjects in group D:

* Confirmation of prior vaccination with BCG not less than three months prior to projected study enrolment date (by visible BCG scar on examination or written documentation)
* Willingness to use continuous effective barrier contraception for three months after receiving MVA85A vaccination (males and females)

Exclusion Criteria:

* Clinical, radiological, or laboratory evidence of current active TB disease
* Laboratory evidence at screening of latent M. tb infection as indicated by a positive ELISPOT test (\>17 sfc/million PBMC) in any ESAT6 peptide or CFP10 peptide poola
* Previous vaccination with candidate TB vaccine MVA85A or candidate TB vaccine FP85A
* Clinically significant history of skin disorder, allergy, immunodeficiency (including HIV), cancer (except BCC or CIS), cardiovascular disease, respiratory 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 study vaccine
* Any abnormality of screening blood or urine tests that is deemed to be clinically significant or that may compromise the safety of the volunteer in the studyb
* Positive HBsAg, HCV or HIV antibodies
* Female currently lactating, confirmed pregnancy or intention to become pregnant during study period
* Use of an investigational medicinal product or non-registered drug, live vaccine, or medical device other than the study vaccine for 60 days prior to dosing with the study vaccine, or planned use during the study 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 volunteer at risk or may influence the result of the study or may affect the volunteer's ability to participate in the study

Additional exclusion criteria for subjects in group A:

* Previous vaccination with BCG

Additional exclusion criteria for subjects in group B:

* Previous vaccination with a recombinant MVA vaccine other than MVA85A or FP85A
* Previous vaccination with BCG

Additional exclusion criteria for subjects in group C:

* None

Additional exclusion criteria for subjects in group D:

* Previous vaccination with a recombinant MVA vaccine other than MVA85A or FP85A
D: Inclusion Criteria

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

* Healthy adolescents aged 12-17 years (both male and female)
* Resident in the study area for the duration of the study period
* Confirmation of prior vaccination with BCG not less than 6 months prior to projected study vaccination date (by visible BCG scar on examination or written documentation)
* No relevant findings in medical history or on physical examination
* Written informed consent by parent or guardian
* Written informed assent by subject
* Refrain from blood donation during the trial
* Agree to avoid pregnancy for the duration of the trial (female only)
* Able and willing (in the Investigator's opinion) to comply with all the study requirements
* Stool sample negative for S. mansoni (group 1) or positive for S. mansoni infection (group 2), based on the results of the Kato Katz stool analysis
* Willing to delay treatment for schistosomiasis for at least one month (group 2)

Exclusion Criteria

Participants may not enter the trial if ANY of the following apply:

* Clinical, radiological, or laboratory evidence of current active TB disease
* Laboratory evidence at screening of latent M. tb infection as indicated by a positive ELISPOT response to ESAT6 or CFP10 antigens
* Previous treatment for active or latent tuberculosis infection
* 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
* Received a TST within 90 days prior to day 0
* Clinically significant history of skin disorder, allergy, immunodeficiency (including HIV), cancer (except BCC or CIS), cardiovascular disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder and neurological illness, drug or alcohol abuse
* History of serious psychiatric condition or disorder
* Concurrent oral or systemic steroid medication or the concurrent use of other immunosuppressive agents within 2 months prior to enrolment
* History of anaphylaxis to vaccination or any allergy likely to be exacerbated by any component of the study 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 volunteer in the study
* Positive HBsAg, HCV or HIV antibodies
* Use of an investigational medicinal product or non-registered drug, live vaccine, or medical device other than the study vaccine for 30 days prior to dosing with the study vaccine, or planned use during the study period
* Administration of immunoglobulins and/or any blood products within the three months preceding the planned trial vaccination date
* Female currently lactating, confirmed pregnancy or intention to become pregnant during the trial period
* Screening blood sample positive for malaria or Mansonella perstans by microscopy
* Schistosoma mansoni infection intensity greater than 2000 eggs per gram of stool
* Any of the three screening stool samples positive for any helminths on Kato Katz examinations or for S. mansoni or Strongyloides stercoralis by PCR (group 1); or any of the three screening stool samples positive for helminths other than S. mansoni on Kato Katz examinations or for Strongyloides stercoralis by PCR (group 2)
* Screening urine sample positive for S. mansoni infection (group 1)
* 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

Answer: A