Working… Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00654316
Recruitment Status : Completed
First Posted : April 7, 2008
Last Update Posted : April 7, 2008
Information provided by:
University of Oxford

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.

Condition or disease Intervention/treatment Phase
TB Biological: BCG Phase 1

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 11 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: A Phase I Study of the Safety and Immunogenicity of BCG (Bacille Calmette-Guerin) Vaccine Delivered Intradermally by a Needle Injection in Healthy Volunteers Who Have Previously Received BCG.
Study Start Date : February 2004
Actual Primary Completion Date : November 2005
Actual Study Completion Date : November 2005

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: 1
BCG delivered intradermally into the deltoid region in volunteers who have received BCG 10 - 20 years previously.
Biological: BCG
intradermal injection of 0.1ml BCG over the deltoid muscle
Other Name: Bacille Calmette-Guerin

Primary Outcome Measures :
  1. The occurence and severity of local side-effects The occurence and severity of systemic side-effects [ Time Frame: 1 year ]

Secondary Outcome Measures :
  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. [ Time Frame: 1 year ]

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

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

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00654316

Layout table for location information
United Kingdom
Centre for Clinical Vaccinology and Tropical Medicine
Oxford, Oxfordshire, United Kingdom, OX3 7LJ
Sponsors and Collaborators
University of Oxford
Layout table for investigator information
Principal Investigator: Helen McShane University of Oxford
Publications automatically indexed to this study by Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Dr Helen McShane, University of Oxford Identifier: NCT00654316    
Other Study ID Numbers: TB006
First Posted: April 7, 2008    Key Record Dates
Last Update Posted: April 7, 2008
Last Verified: March 2008
Keywords provided by University of Oxford: