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 With no Evidence of Infection With Mycobacterium Tuberculosis, in Cape Town
Brief Summary: This study is designed to evaluate the safety of MVA85A in healthy volunteers in Cape Town. We have shown that MVA85A is safe and immunogenic in both a mycobacterially naïve population in the UK and in a more mycobacterially exposed population in The Gambia. The studies described here will be to assess the safety of MVA85A in 2 groups of adults, those with and without prior BCG vaccination. Once safety data has been obtained in these 2 groups, we will assess the safety of MVA85A in adolescents who have been previously vaccinated with BCG.


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/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 antibody test, HCV antibody test or positive HBV serology except post-vaccination.
* Heaf test greater than Grade 0
* Confirmed pregnancy
* Previous MVA immunisations
B: 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
C: Inclusion Criteria:

* Healthy adults aged 18 to 50 years (for the first 2 arms)
* Healthy adolescents (aged 12-14) for the third arm of the study
* Screening Elispot negative (less than 17 spots/million PBMC) in all 3 ESAT6 pools and all 3 CFP10 pools
* Mantoux test \<15mm (\<10mm if BCG naïve)
* CXR normal with no evidence of active or past TB
* 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 test

Exclusion Criteria:

* Any deviation from the normal range in biochemistry or haematology blood tests or in urine analysis as defined in Appendix I
* Mantoux \>15mm
* 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.)
* 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 diabetes mellitus
* Chronic or active neurological disease requiring ongoing specialist or medical supervision
* Chronic gastrointestinal disease requiring ongoing specialist or medical supervision
* History of \> 2 hospitalisations for invasive bacterial infections (pneumonia, meningitis)
* 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)
* Seropositive for hepatitis C virus (antibodies to HCV)
* Evidence of serious psychiatric condition
* Any other on-going chronic illness requiring hospital specialist or medical supervision
* Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate
* Pregnant or lactating female
* Female who is willing or intends to become pregnant during the study
* Any history of anaphylaxis in reaction to vaccination
* Inability to give informed consent
* 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
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. 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

Answer: C