T-Cell Turnover Following Vaccination With MVA85A

NCT ID: NCT00548444

Last Updated: 2010-01-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-10-31
• Study Completion Date: 2010-01-31

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.

Conditions

Tuberculosis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Group 1

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

Group Type: EXPERIMENTAL

MVA85A

Intervention Type: BIOLOGICAL

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

Group 2

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

Group Type: EXPERIMENTAL

MVA85A

Intervention Type: BIOLOGICAL

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

Deuterated glucose infusion

Intervention Type: 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 3

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

Group Type: EXPERIMENTAL

MVA85A

Intervention Type: BIOLOGICAL

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

Deuterated glucose infusion

Intervention Type: 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).

Interventions

MVA85A

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

Intervention Type: BIOLOGICAL

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).

Intervention Type: OTHER

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Wellcome Trust

OTHER

Sponsor Role: collaborator

St George's, University of London

OTHER

Sponsor Role: collaborator

University of Oxford

OTHER

Sponsor Role: lead

Responsible Party

Clinical Trials and Research Governance Office, University of Oxford

Principal Investigators

Helen I McShane, MBBS, MRCP, BSc, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Oxford

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

Role: STUDY_CHAIR

University of Oxford

Locations

University of Oxford

Oxford, Oxfordshire, United Kingdom

Countries

United Kingdom

References

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.

Reference Type: BACKGROUND

PMID: 15249595 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 16955142 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 17483473 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15502839 (View on PubMed)

Other Identifiers

EudraCT number: 2007-001293-8

Identifier Type: -

Identifier Source: secondary_id

TB018

Identifier Type: -

Identifier Source: org_study_id