TB023: Assessing vaccine-induced immunity with a BCG challenge model

• Research type

  Research Study

• Full title

  A phase 1 study to evaluate a BCG challenge model as a method of assessing anti-mycobacterial immunity induced by BCG and a candidate TB vaccine, MVA85A, alone and in combination.

• IRAS ID

  45004

• Contact name

  Helen McShane

• Sponsor organisation

  University of Oxford

• Eudract number

  2010-018425-19

• ISRCTN Number

  n/a

• Clinicaltrials.gov Identifier

  n/a

• Research summary

  Tuberculosis (TB) is responsible for more deaths worldwide than any other infectious disease. The currently used TB vaccine, BCG (Bacille Calmette-Guerin), is not effective enough at preventing infection in many parts of the world. Therefore a more universally effective vaccination programme is urgently needed. The most advanced new candidate in this field is vaccine MVA85A, developed by the University of Oxford, and currently being tested in a BCG-prime MVA85A-boost regimen in a large phase IIb efficacy trial in infants in South Africa. A major challenge in the field of TB vaccine research is to develop laboratory measures of human immune responses that correlate strongly with protection from TB in order to help distinguish between new vaccines undergoing phase 1 trials. A recent pilot study, TB015, conducted by our group, has established that the BCG 'challenge' model is practically feasible and could be useful for identifying better correlates of protection. The rationale behind this BCG 'challenge' model is that we cannot use Mycobacterium tuberculosis (the bacterium that causes TB in humans) itself as a challenge agent but we can use BCG, a weakened live strain of Mycobacterium bovis (the bacterium that causes TB in cattle), instead. BCG is injected under the skin just like during vaccination, and the injection site is biopsied two weeks later. The quantity of BCG remaining in the biopsy tissue is then measured. An effective vaccine against TB should also be effective against BCG. Thus biopsies of individuals with pre-existing immunity to TB induced by vaccination should contain fewer BCG bacteria than vaccination-naive individuals. We intend to test this model in four groups of 12 individuals receiving no vaccine, prior BCG alone, MVA85A alone, or both vaccines. This exploratory study could lead to the development of better correlates of protection for use in future TB vaccine trials.

• REC name

  South Central - Berkshire Research Ethics Committee

• REC reference

  10/H0505/31

• Date of REC Opinion

  15 Apr 2010

• REC opinion

  Further Information Favourable Opinion