Study of the Safety and Immunogenicity of Bacille Calmette Guerin (BCG) Vaccine

NCT00654316 | Completed Phase 1 DMC

• 1 other identifier: TB006
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

Tuberculosis (TB) kills about three million people annually. It is estimated that one third of the world's population are latently infected with Mycobacterium tuberculosis (M.tb). Multi-drug resistant strains of M.tb, and co-infection with M.tb and HIV present major new challenges. The currently available vaccine, M. bovis BCG, is largely ineffective at protecting against adult pulmonary disease in endemic areas and it is widely agreed that a new more effective tuberculosis vaccine is a major global public health priority1. However, it may be unethical and impractical to test and deploy a vaccine strategy that does not include BCG, as BCG does confer worthwhile protection against TB meningitis and leprosy. An immunisation strategy that includes BCG is also attractive because the populations in which this vaccine candidate will need to be tested will already have been immunised with BCG. M.tb is an intracellular organism. CD4+ Th1-type cellular responses are essential for protection and there is increasing evidence from animal and human studies that CD8+ T cells also play a protective role2. However, it has generally been difficult to induce strong cellular immune responses in humans using subunit vaccines. DNA vaccines induce both CD4+ and CD8+ T cells and thus offer a potential new approach to a TB vaccine. DNA vaccines encoding various antigens from M. tuberculosis have been evaluated in the murine model, and to date no DNA vaccine alone has been shown to be superior to BCG. A heterologous prime-boost immunisation strategy involves giving two different vaccines, each encoding the same antigen, several weeks apart. Such regimes are extremely effective at inducing a cellular immune response. Using a DNA- prime/MVA-boost immunisation strategy induces high levels of CD8+ T cells in animal models of malaria and HIV5, and high levels of both CD4+ and CD8+ T cells in animal models of TB. BCG immunisation alone induces only CD4+ T cells in mice. A prime-boost strategy using BCG as the prime and a recombinant MVA encoding an antigen from M.tb that is also present in BCG (antigen 85A: 'MVA85A') as the boost, induces much higher levels of CD4+ T cells than BCG or MVA85A alone. In addition, this regime generates specific CD8+ T cells that are undetectable following immunisation with BCG alone.

Conditions

TB

Keywords

TB; Tuberculosis; MVA85A; Vaccine; BCG

Outcome Measures

Primary Outcomes (1)

• The occurence and severity of local side-effects The occurence and severity of systemic side-effects

  1 year

Secondary Outcomes (1)

• The induction of T cell responses (as measured by an interferon-gamma Elispot assay). Other exploratory cellular immunology assays will be performed as such assays are developed.

  1 year

Study Arms (1)

1

EXPERIMENTAL

BCG delivered intradermally into the deltoid region in volunteers who have received BCG 10 - 20 years previously.

Biological: BCG

Interventions

BCG BIOLOGICAL

intradermal injection of 0.1ml BCG over the deltoid muscle

Also known as: Bacille Calmette-Guerin

1

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy adult aged 18-55 years.
• Normal medical history and physical examination.
• Normal urine dipstick, blood count, liver enzymes, and creatinine.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Oxford: lead

Study Sites (1)

Centre for Clinical Vaccinology and Tropical Medicine

Oxford, Oxfordshire, OX3 7LJ, United Kingdom

Location

Related Publications (3)

• McShane H, Brookes R, Gilbert SC, Hill AV. Enhanced immunogenicity of CD4(+) t-cell responses and protective efficacy of a DNA-modified vaccinia virus Ankara prime-boost vaccination regimen for murine tuberculosis. Infect Immun. 2001 Feb;69(2):681-6. doi: 10.1128/IAI.69.2.681-686.2001.

  PMID: 11159955 BACKGROUND

• McShane H, Behboudi S, Goonetilleke N, Brookes R, Hill AV. Protective immunity against Mycobacterium tuberculosis induced by dendritic cells pulsed with both CD8(+)- and CD4(+)-T-cell epitopes from antigen 85A. Infect Immun. 2002 Mar;70(3):1623-6. doi: 10.1128/IAI.70.3.1623-1626.2002.

  PMID: 11854254 BACKGROUND

• Whelan KT, Pathan AA, Sander CR, Fletcher HA, Poulton I, Alder NC, Hill AV, McShane H. Safety and immunogenicity of boosting BCG vaccinated subjects with BCG: comparison with boosting with a new TB vaccine, MVA85A. PLoS One. 2009 Jun 16;4(6):e5934. doi: 10.1371/journal.pone.0005934.

  PMID: 19529780 DERIVED

MeSH Terms

Conditions

Tuberculosis

Condition Hierarchy (Ancestors)

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

Study Officials

• Helen McShane

  University of Oxford

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: April 2, 2008
• First Posted: April 7, 2008
• Study Start: February 1, 2004
• Primary Completion: November 1, 2005
• Study Completion: November 1, 2005
• Last Updated: April 7, 2008

Record last verified: 2008-03

Locations

GB (1)