Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase I Study of the Safety and Immunogenicity of MVA85A in Healthy Gambian Volunteers
Brief Summary: A Phase I study of the Safety and immunogenicity of MVA85A in healthy Gambian volunteers


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:

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 male aged 18-45 years.
* Normal medical history and physical examination. Minor physical ailments e.g. Fungal skin infections, will not be sufficient to define a physical examination as abnormal.
* Normal urine dipstick, blood count, liver enzymes, and creatinine
* Frequency \<4 SFU per/well/3x105 PBMC as determined by ELISPOT with ESAT6/CFP-10 antigens and less than 100 SFU per/well/1x106 PBMC as determined by ELISPOT with PPD.
* Mantoux negative (0.0 mm induration).
* Normal Chest X-ray.
* Willing to donate blood samples as required by the protocol

Exclusion Criteria:

* Clinically significant history of skin disorder (eczema, psoriasis, etc.), allergy, immunodeficiency, cardiovascular disease, respiratory disease, endocrine disorder, liver disease, renal disease, gastrointestinal disease or neurological illness.
* Any clinical evidence of immunosuppression such as oral candida, stomatitis, aphthous or septic ulceration, septic skin lesions or any clinical or laboratory evidence of infection or immunocompromise.
* History of splenectomy
* Haematocrit of less than 30%
* Serum creatinine concentration \>130mmol
* Serum ALT concentration \>80IU/L
* Blood transfusion within one month of the beginning of the study
* History of vaccination with any previous experimental poxvirus vaccine
* Administration of any other vaccine or immunoglobulin within two weeks before or two weeks after vaccination.
* Positive HIV antibody test, evidence of HBV (Hepatitis B vaccination is not an exclusion criteria)..
* Current participation in another clinical trial, or within 12 weeks of this study
* Any other finding which in the opinion of the investigators would increase the risk of an adverse outcome from participation in the trial.
* Likelihood of travel away from the study area for the duration of the study
* Untreated malaria infection
D: 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

Answer: C