T-Cell Turnover Following Vaccination With MVA85A

NCT00548444 | Completed Phase 1

• 2 other identifiers: TB018EudraCT number: 2007-001293-8
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Tuberculosis

Keywords

Tuberculosis; Lymphocyte kinetics; MVA85A; Deuterium

Outcome Measures

Primary Outcomes (1)

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

  Within four weeks of vaccination

Secondary Outcomes (2)

• Immunogenicity

  Within three months of vaccination

• Safety

  Within three months of vaccination

Study Arms (3)

Group 1

EXPERIMENTAL

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

Biological: MVA85A

Group 2

EXPERIMENTAL

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

Biological: MVA85A; Other: Deuterated glucose infusion

Group 3

EXPERIMENTAL

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

Biological: MVA85A; Other: Deuterated glucose infusion

Interventions

MVA85A BIOLOGICAL

Vaccine. Dose: 1 x 10\^8 plaque-forming units (pfu) given by intradermal injection into the deltoid region of the upper arm.

Group 1; Group 2; Group 3

Deuterated glucose infusion OTHER

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).

Group 2; Group 3

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Oxford: lead
• Wellcome Trust: collaborator
• St George's, University of London: collaborator

Study Sites (1)

University of Oxford

Oxford, Oxfordshire, OX3 7LJ, United Kingdom

Location

Related Publications (4)

• 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.

  PMID: 15249595 BACKGROUND

• 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.

  PMID: 16955142 BACKGROUND

• 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.

  PMID: 17483473 BACKGROUND

• 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.

  PMID: 15502839 BACKGROUND

MeSH Terms

Conditions

Tuberculosis

Interventions

MVA 85A

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• Helen I McShane, MBBS, MRCP, BSc, PhD

  University of Oxford

  PRINCIPAL INVESTIGATOR

• Adrian VS Hill, MA, BM BCh, DPhil, DM

  University of Oxford

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: October 23, 2007
• First Posted: October 24, 2007
• Study Start: October 1, 2007
• Primary Completion: January 1, 2010
• Study Completion: January 1, 2010
• Last Updated: January 18, 2010

Record last verified: 2010-01

Locations

GB (1)