T−Cell Turnover Following Vaccination With MVA85A

This study has been completed.
Sponsor:
Collaborators:
Wellcome Trust
St George's, University of London
Information provided by:
University of Oxford
ClinicalTrials.gov Identifier:
NCT00548444
First received: October 23, 2007
Last updated: January 15, 2010
Last verified: January 2010
  Purpose

This study examines the early immune response to a new vaccine (MVA85A) being developed to combat tuberculosis (TB).


Condition Intervention Phase
Tuberculosis
Biological: MVA85A
Other: Deuterated glucose infusion
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Measurement of Human T−Cell Turnover Following Vaccination With the Tuberculosis Vaccine MVA85A

Resource links provided by NLM:


Further study details as provided by University of Oxford:

Primary Outcome Measures:
  • Proliferation and disappearance rates of responding antigen-specific T-cells [ Time Frame: Within four weeks of vaccination ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Immunogenicity [ Time Frame: Within three months of vaccination ] [ Designated as safety issue: No ]
  • Safety [ Time Frame: Within three months of vaccination ] [ Designated as safety issue: Yes ]

Enrollment: 12
Study Start Date: October 2007
Study Completion Date: January 2010
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1
Volunteers will receive a single dose of MVA85A followed by regular blood tests to measure the resulting cellular immune response.
Biological: MVA85A
Vaccine. Dose: 1 x 10^8 plaque-forming units (pfu) given by intradermal injection into the deltoid region of the upper arm.
Experimental: Group 2
Volunteers will receive a single dose of MVA85A followed by an infusion of labelled (deuterated) glucose and regular blood tests.
Biological: MVA85A
Vaccine. Dose: 1 x 10^8 plaque-forming units (pfu) given by intradermal injection into the deltoid region of the upper arm.
Other: Deuterated glucose infusion
6,6D2-glucose given as a timed intravenous infusion. The total dose of deuterated glucose will be 1g/kg volunteer body weight (up to a maximum of 60g).
Experimental: Group 3
Volunteers will receive a single dose of MVA85A followed by an infusion of labelled (deuterated) glucose and regular blood tests.
Biological: MVA85A
Vaccine. Dose: 1 x 10^8 plaque-forming units (pfu) given by intradermal injection into the deltoid region of the upper arm.
Other: Deuterated glucose infusion
6,6D2-glucose given as a timed intravenous infusion. The total dose of deuterated glucose will be 1g/kg volunteer body weight (up to a maximum of 60g).

Detailed Description:

MVA85A is a promising new vaccine designed to prevent tuberculosis (TB) by dramatically boosting pre-existing responses to BCG, the only licensed vaccine against the disease at present. In BCG vaccinated individuals it induces a strong immune response. However little is known about the evolution of that response or of the kinetics of T-cells (the immune cells that respond to the vaccine) immediately following vaccination. Crucially, the outcome of this process may determine long term protection from disease.

This study aims to define the early immune response to MVA85A and is the first to apply a safe, non-radioactive 'label' - deuterium - to measure T-cell turnover following vaccination. This labelling approach has been used successfully by the study collaborators to examine immune cell kinetics in human clinical studies in the UK over the last 8 years. The resulting data will provide insight into the immune response generated by MVA85A and aid in the future design and modification of other T-cell inducing vaccines.

Group 1 (Immune responses only)

Previous human studies of MVA85A have described the immune response to vaccination at fixed timepoints but not in between. The investigators will vaccinate four volunteers and measure immune responses daily for 14 days. This will provide important new data and aid interpretation of kinetics data from groups 2 and 3.

Groups 2 & 3 (Labelling)

Eight volunteers will be vaccinated and then receive a timed infusion of deuterated glucose. Blood will be collected during the follow up period to determine the rates of uptake and loss of label in responding immune cells.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy adult aged 18 to 50 years
  • Immunization with BCG greater than 12 months prior to enrolment in the study
  • Resident in or near Oxford for the duration of the study
  • Able and willing (in the investigator's opinion) to comply with all study requirements
  • Given written informed consent
  • Willing to allow the investigator to request medical information from, or discuss the volunteer's medical history with the volunteer's General Practitioner
  • Willing to allow the investigator to register volunteer details with a confidential database to prevent concurrent entry into clinical trials
  • For women only, willingness to practice continuous effective contraception during the study
  • Agreement to refrain from blood donation during the course of the study

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 vaccine
  • Screening test suggesting the possibility of latent TB infection- i.e. Elispot positive (greater than 17 sfc/million PBMC) in any ESAT6 peptide or CFP10 peptide pool
  • Any clinically significant abnormal finding on screening blood tests or urinalysis (see Appendix B for guidance on study reference ranges)
  • 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
  • History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ)
  • History of serious psychiatric condition
  • 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) or hepatitis C virus (antibodies to HCV)
  • Pregnancy, lactation or willingness/intention to become pregnant during the study
  • Any other chronic illness requiring hospital specialist supervision
  • Any other significant disease, disorder or finding, which, in the opinion of the investigator, 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 fully in the study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00548444

Locations
United Kingdom
University of Oxford
Oxford, Oxfordshire, United Kingdom, OX3 7LJ
Sponsors and Collaborators
University of Oxford
Wellcome Trust
St George's, University of London
Investigators
Principal Investigator: Helen I McShane, MBBS, MRCP, BSc, PhD University of Oxford
Study Chair: Adrian VS Hill, MA, BM BCh, DPhil, DM University of Oxford
  More Information

Publications:
Responsible Party: Ms. Heather House, Head, Clinical Trials and Research Governance Office, University of Oxford
ClinicalTrials.gov Identifier: NCT00548444     History of Changes
Other Study ID Numbers: TB018, EudraCT number: 2007−001293-8
Study First Received: October 23, 2007
Last Updated: January 15, 2010
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Department of Health
United Kingdom: Research Ethics Committee

Keywords provided by University of Oxford:
Tuberculosis
Lymphocyte kinetics
MVA85A
Deuterium

Additional relevant MeSH terms:
Tuberculosis
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections

ClinicalTrials.gov processed this record on July 26, 2014