TB043: Investigating immune responses to aerosol BCG challenge
Research type
Research Study
Full title
A human challenge study to evaluate innate and adaptive immune responses to a controlled human infection with BCG administered by the aerosol inhaled route in healthy, BCG-naïve, UK adult volunteers
IRAS ID
246087
Contact name
Helen McShane
Contact email
Sponsor organisation
University of Oxford
Duration of Study in the UK
1 years, 11 months, 30 days
Research summary
Mycobacterium tuberculosis (M.tb) is a pathogen with worldwide preponderance that infects humans and causes the transmissible disease tuberculosis (TB). An estimated one-third of the world’s population is latently infected with M.tb, carrying a 10% lifetime risk of developing active life-threatening disease. In 2016, there were 10 million new cases worldwide and 1.7 million people died of TB. Co-infection with human immunodeficiency virus (HIV) greatly increases the risk of TB reactivation and death. Diagnosis is challenging and drug treatment is often harmful, costly and complex. Furthermore, an improved understanding of the nature of protective immunity in humans would significantly improve rational vaccine development.
Three studies to date have evaluated BCG as a challenge agent via intradermal injection into the upper arm, and one of our previous trials (TB041) has administered aerosol BCG as a controlled challenge. The natural route of infection for M.tb is by inhalation of infectious droplets, leading to infection in the lung. The lung has it own distinct mucosal immune system and therefore administering BCG challenge (as in TB041) directly to the lungs more closely represents TB infection than an injection of BCG in the arm.
This trail will involve 65 subjects across five groups, with 50 individuals receiving aerosol BCG (1x10^7cfu-the dose used in TB041) and 15 receiving aerosol saline placebo. We will perform bronchoscopies on all individuals at different time points (2,7,14,28,or 56 days) post-challenge/placebo administration to collect bronchoalveolar lavage (BAL) to measure the amount of BCG recovered from the lungs. Blood tests to look at immunological markers will be taken to identify correlates of protection against the infection.
The trial will take place at the Centre for Clinical Vaccinology and Tropical Medicine and the OUH NHS Foundation Trust, Oxford.
REC name
South Central - Oxford A Research Ethics Committee
REC reference
18/SC/0307
Date of REC Opinion
20 Sep 2018
REC opinion
Further Information Favourable Opinion