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 Asymptomatic Volunteers Who Are Infected With Either Mycobacterium Tuberculosis (M.tb.), Human Immunodeficiency Virus (HIV) or Both
Brief Summary: This study is designed to evaluate the safety of MVA85A in asymptomatic volunteers in South Africa who are infected with M.tb, HIV or both. A single vaccination with MVA85A, when administered at a dose of 5 x 107pfu intradermally, is safe and highly immunogenic in mycobacterially naïve individuals, BCG vaccinated individuals and M.tb latently infected individuals. We will use the same vaccination regime in this study. Participants will be defined as being infected with M.tb.if they have a positive Elispot response to ESAT6 or CFP10. Participants will be defined as being infected with HIV.if they have a positive HIV rapid test (Determine®, Abbott Laboratories) followed by a positive HIV ELISA result. Participants will be identified from the general population living in Worcester, Western Cape, South Africa


Options:
A: Inclusion Criteria:

* Healthy adult aged 18-65 years.
* Normal medical history and physical examination.
* Normal urine dipstick, blood count, liver enzymes, and creatinine.

Exclusion Criteria:

* Exposure to TB/BCG vaccination 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 or core HBV antibody test.
* Positive Heaf test
* Positive ANA or serum anti-DNA antibody.
* Confirmed pregnancy
B: Inclusion Criteria:

For all groups:

* Asymptomatic adults aged 21 to 50 years
* Chest x-ray normal with no evidence of past/present TB infection or disease or any other clinically significant finding
* Resident in or near Worcester for the duration of the vaccination study
* Willingness to allow the investigators to discuss the volunteer's medical history with the
* volunteer's usual doctor or HIV physician
* Agreement to refrain from blood donation during the course of the study
* Willing and able to provide written informed consent
* Willingness to undergo an HIV test

For the M.Tb infected- and M.Tb/HIV coinfected- groups:

• Screening Elispot positive (more than 50 spots/million PBMC): for either the pool of ESAT6 peptides and/or the pool of CFP10 peptides and screening Elispot positive for PPD.

• Positive Mantoux test. (\>10mm induration)

For the HIV infected and M.Tb/HIV coinfected groups:

* HIV antibody positive; diagnosed at least 3 months previously
* CD4 count \>300; nadir CD4 not \< 300

Exclusion Criteria:

For all groups:

* Any deviation from the normal range in biochemistry or haematology blood tests or in urine analysis that is considered to be clinically significant
* Any previous ARV therapy
* 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.)
* Pregnant/lactating female and any female who is willing or intends to become pregnant during the study
* Any AIDS defining illness
* History of allergic disease or reactions likely to be exacerbated by any component of the vaccine, e.g. egg products
* Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 42 units every week
* Seropositive for hepatitis B surface antigen (HBsAg) and or hepatitis C (antibodies to HCV)
* 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)
* Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate
* Any history of anaphylaxis in reaction to vaccination
* PI assessment of lack of willingness to participate and comply with all requirements of the protocol
* Any other finding which in the opinion of the investigator would significantly increase the risk of having an adverse outcome from participating in this protocol

For the M.Tb infected group (but not the HIV infected and M.Tb/HIV coinfected groups):

* Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection and asplenia

For the HIV infected and M.Tb/HIV coinfected groups (but not the M.Tb infected/HIV uninfected group)

* CD4 count now more than 300 and CD4 nadir not less than 300
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:

* HIV infected mother receiving either cART, or started on PMTCT prophylaxis
* Maternal antenatal and post-natal written informed consent;
* Maternal age 18 years or older at the time of informed consent;
* Infant age \< 96 hours;
* Infant birth and residence in the study area;
* Mother contactable and able to attend follow-up visits.

Exclusion Criteria:

* Neonatal Apgar score \< 7 at 5 minutes;
* Infant birth weight \< 2,000g or \> 4,500g;
* Estimated infant gestational age \< 32 weeks;
* Neonatal respiratory distress;
* History or evidence of infant congenital abnormality, or immunosuppressive condition, other than HIV infection;
* Any maternal or infant condition or systemic illness that in the opinion of the investigator is likely to affect safety or immunogenicity of study vaccine;
* Infant BCG vaccination prior to enrollment;
* Residence in a household, or frequent close contact, with an adult diagnosed with active TB who has not yet completed TB treatment;
* Mother with active TB who has not yet completed TB treatment;
* Unknown or negative maternal HIV status;
* Intention to leave the study area and/or unable to attend follow-up visits.

Answer: B