结核病,牛津大学

Detailed Description
The need for new vaccine against tuberculosisTuberculosis(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) (Dye, 1999). These latently infected individuals are at risk of reactivation of infection, should they becomeimmunosuppressed. Worldwide,coinfectionwith HIV is the commonest cause ofimmunosuppressionand increases the chances of reactivation from a 10% lifetime risk to a 10% annual risk (Corbett, 1996). The currently available vaccine, M.bovisBCG, 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 priority (Colditz, 1994). 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. Animmunisationstrategy that includes BCG is also attractive because the populations in which this vaccine candidate will need to be tested will already have beenimmunisedwith BCG. Given the high prevalence of infection withM.tb, a vaccine that could be administered to latently infected individuals and eradicate latent infection would have an enormous impact on the mortality and morbidity from TB.M.tbis 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 role (Flynn, 2001). However, it has generally been difficult to induce strong cellular immune responses in humans using subunit vaccines. DNA vaccines, recombinant viral vectors and protein/adjuvant combinations all induce both CD4+ and CD8+ Tcells,however none of these antigen delivery systems induce high levels of antigen specific T cells, when used alone.
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Tracking Information
First Received DateICMJE
November 2, 2006
The Safety and Immunogenicity of aTBVaccine; MVA85A, in Healthy Volunteers Who Are Infected With HIV
Official TitleICMJE
A Phase I Study Evaluating the Safety and Immunogenicity of a NewTBVaccine, MVA85A, in Healthy Volunteers Who Are Infected With HIV
The Safety and Immunogenicity of a TB Vaccine; MVA85A, in Healthy Volunteers Who Are Infected With HIV
This study has been completed.
Sponsor:
University of Oxford
(submitted: April 2, 2008)
Immune responses [ Time Frame: 1 year ] [ Designated as safety issue: No ]
Original Secondary Outcome MeasuresICMJE
(submitted: November 2, 2006)
Last Updated Date
March 25, 2011
Start DateICMJE
November 2006
Primary Completion Date
July 2010 (final data collection date for primary outcome measure)
Current Primary Outcome MeasuresICMJE
(submitted: April 2, 2008)
Data on adverse events [ Time Frame: 1 year ] [ Designated as safety issue: No ]
Original Primary Outcome MeasuresICMJE
(submitted: November 2, 2006)
Information provided by:
University of Oxford
Identifier:
NCT00395720
First received: November 2, 2006
Last updated: March 25, 2011
Last verified: March 2011
Data on adverse events
ete list of historical versions of study NCT00395720 on Archive Site
Current Secondary Outcome MeasuresICMJE
Heterologousprime-boostimmunisationstrategies involve giving two different vaccines, each encoding the same antigen, several weeks apart. Using a DNA prime-recombinant modifiedvacciniavirus Ankara (MVA) boost induces higher levels of antigen specific CD4+ and CD8+ T cells than using homologous boostingwith the same vector in a number of different disease models (Schneider, 1998;McShane, 2001). Given the protective efficacy of BCG in childhood, ideally BCG would be the primingimmunisationin such a prime-boost strategy. In order to do this, we have focused on antigen 85A as a candidate antigen. Antigen 85A is highly conserved amongst allmycobacterialspecies and is present in all strains of BCG. Antigen 85A is a major secreted antigen from M. tuberculosis which forms part of the antigen 85 complex (A, B and C). This complex constitutes a major portion of the secreted proteins of bothM.tband BCG. It is involved infibronectinbinding within the cell wall and hasmycolyltransferaseactivity. Antigen 85A isimmunodominantinmurineand human studies and is protective in small animals (Huygen, 1996).