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T-Cell Turnover Following Vaccination With MVA85A

Primary Purpose

Tuberculosis

Status
Completed
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
MVA85A
Deuterated glucose infusion
Sponsored by
University of Oxford
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Tuberculosis focused on measuring Tuberculosis, Lymphocyte kinetics, MVA85A, Deuterium

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • University of Oxford

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Group 1

Group 2

Group 3

Arm Description

Volunteers will receive a single dose of MVA85A followed by regular blood tests to measure the resulting cellular immune response.

Volunteers will receive a single dose of MVA85A followed by an infusion of labelled (deuterated) glucose and regular blood tests.

Volunteers will receive a single dose of MVA85A followed by an infusion of labelled (deuterated) glucose and regular blood tests.

Outcomes

Primary Outcome Measures

Proliferation and disappearance rates of responding antigen-specific T-cells

Secondary Outcome Measures

Immunogenicity
Safety

Full Information

First Posted
October 23, 2007
Last Updated
January 15, 2010
Sponsor
University of Oxford
Collaborators
Wellcome Trust, St George's, University of London
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1. Study Identification

Unique Protocol Identification Number
NCT00548444
Brief Title
T-Cell Turnover Following Vaccination With MVA85A
Official Title
Measurement of Human T-Cell Turnover Following Vaccination With the Tuberculosis Vaccine MVA85A
Study Type
Interventional

2. Study Status

Record Verification Date
January 2010
Overall Recruitment Status
Completed
Study Start Date
October 2007 (undefined)
Primary Completion Date
January 2010 (Actual)
Study Completion Date
January 2010 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
University of Oxford
Collaborators
Wellcome Trust, St George's, University of London

4. Oversight

Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tuberculosis
Keywords
Tuberculosis, Lymphocyte kinetics, MVA85A, Deuterium

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
12 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group 1
Arm Type
Experimental
Arm Description
Volunteers will receive a single dose of MVA85A followed by regular blood tests to measure the resulting cellular immune response.
Arm Title
Group 2
Arm Type
Experimental
Arm Description
Volunteers will receive a single dose of MVA85A followed by an infusion of labelled (deuterated) glucose and regular blood tests.
Arm Title
Group 3
Arm Type
Experimental
Arm Description
Volunteers will receive a single dose of MVA85A followed by an infusion of labelled (deuterated) glucose and regular blood tests.
Intervention Type
Biological
Intervention Name(s)
MVA85A
Intervention Description
Vaccine. Dose: 1 x 10^8 plaque-forming units (pfu) given by intradermal injection into the deltoid region of the upper arm.
Intervention Type
Other
Intervention Name(s)
Deuterated glucose infusion
Intervention Description
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).
Primary Outcome Measure Information:
Title
Proliferation and disappearance rates of responding antigen-specific T-cells
Time Frame
Within four weeks of vaccination
Secondary Outcome Measure Information:
Title
Immunogenicity
Time Frame
Within three months of vaccination
Title
Safety
Time Frame
Within three months of vaccination

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Helen I McShane, MBBS, MRCP, BSc, PhD
Organizational Affiliation
University of Oxford
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Adrian VS Hill, MA, BM BCh, DPhil, DM
Organizational Affiliation
University of Oxford
Official's Role
Study Chair
Facility Information:
Facility Name
University of Oxford
City
Oxford
State/Province
Oxfordshire
ZIP/Postal Code
OX3 7LJ
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
15249595
Citation
Macallan DC, Wallace D, Zhang Y, De Lara C, Worth AT, Ghattas H, Griffin GE, Beverley PC, Tough DF. Rapid turnover of effector-memory CD4(+) T cells in healthy humans. J Exp Med. 2004 Jul 19;200(2):255-60. doi: 10.1084/jem.20040341. Epub 2004 Jul 12.
Results Reference
background
PubMed Identifier
16955142
Citation
Vukmanovic-Stejic M, Zhang Y, Cook JE, Fletcher JM, McQuaid A, Masters JE, Rustin MH, Taams LS, Beverley PC, Macallan DC, Akbar AN. Human CD4+ CD25hi Foxp3+ regulatory T cells are derived by rapid turnover of memory populations in vivo. J Clin Invest. 2006 Sep;116(9):2423-33. doi: 10.1172/JCI28941. Erratum In: J Clin Invest. 2006 Oct;116(10):2829-30.
Results Reference
background
PubMed Identifier
17483473
Citation
Asquith B, Zhang Y, Mosley AJ, de Lara CM, Wallace DL, Worth A, Kaftantzi L, Meekings K, Griffin GE, Tanaka Y, Tough DF, Beverley PC, Taylor GP, Macallan DC, Bangham CR. In vivo T lymphocyte dynamics in humans and the impact of human T-lymphotropic virus 1 infection. Proc Natl Acad Sci U S A. 2007 May 8;104(19):8035-40. doi: 10.1073/pnas.0608832104. Epub 2007 May 1.
Results Reference
background
PubMed Identifier
15502839
Citation
McShane H, Pathan AA, Sander CR, Keating SM, Gilbert SC, Huygen K, Fletcher HA, Hill AV. Recombinant modified vaccinia virus Ankara expressing antigen 85A boosts BCG-primed and naturally acquired antimycobacterial immunity in humans. Nat Med. 2004 Nov;10(11):1240-4. doi: 10.1038/nm1128. Epub 2004 Oct 24. Erratum In: Nat Med. 2004 Dec;10(12):1397.
Results Reference
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T-Cell Turnover Following Vaccination With MVA85A

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