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

This study has been completed.
Sponsor:
Information provided by:
University of Oxford
ClinicalTrials.gov Identifier:
NCT00654316
First received: April 2, 2008
Last updated: April 4, 2008
Last verified: March 2008
  Purpose

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 Intervention Phase
TB
Biological: BCG
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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.

Resource links provided by NLM:


Further study details as provided by University of Oxford:

Primary Outcome Measures:
  • The occurence and severity of local side-effects The occurence and severity of systemic side-effects [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 11
Study Start Date: February 2004
Study Completion Date: November 2005
Primary Completion Date: November 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00654316

Locations
United Kingdom
Centre for Clinical Vaccinology and Tropical Medicine
Oxford, Oxfordshire, United Kingdom, OX3 7LJ
Sponsors and Collaborators
University of Oxford
Investigators
Principal Investigator: Helen McShane University of Oxford
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Dr Helen McShane, University of Oxford
ClinicalTrials.gov Identifier: NCT00654316     History of Changes
Other Study ID Numbers: TB006
Study First Received: April 2, 2008
Last Updated: April 4, 2008
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by University of Oxford:
TB
Tuberculosis
MVA85A
Vaccine
BCG

ClinicalTrials.gov processed this record on April 23, 2014