The University of Oxford in partnership with the Coler Lab at Seattle Children's Research Institute (SCRI) has begun a new clinical trial called TB045, which aims to test tuberculosis (TB) vaccine safety and the host immune response in a first-in-man aerosol mycobacterial challenge infection model with healthy adult volunteers.
TB is a disease caused by the bacterium Mycobacterium tuberculosis and in 2023 was the leading cause of death from an infectious disease globally. The only current licensed vaccine against TB is Bacillus Calmette-Guérin (BCG), which has remained unchanged for over a century. BCG is a weakened form of Mycobacterium bovis, which is very similar to Mycobacterium tuberculosis and is normally given as an injection in the skin at birth in areas with endemic TB. Although BCG is safe to give to infants, it does not provide life-long protection and drugs against TB are not enough to stop the financial and social burden of TB. An effective vaccine is urgently needed to reduce the spread of TB, prevent progression to active disease, and save lives.
The Jenner Institute at the University of Oxford is developing a pioneering human challenge model to test new TB vaccines. A challenge model is used to test if new vaccines work, before larger field (efficacy) studies. These models have been used to test other vaccines such as malaria, where volunteers are purposefully given malaria after the trial vaccine to see if the vaccine works. In this challenge model, volunteers will be given BCG as a representative mycobacterium aerosol challenge, as it would not be ethical to give study participants live Mycobacterium tuberculosis.
In this study 24 volunteers will receive the new TB vaccine (called ID93+GLA-SE) and 24 volunteers will receive no vaccine at all (control group). All of the volunteers will then be challenged with BCG to assess the immune response to ID93+GLA-SE vaccine after an aerosol mycobacterial challenge. The volunteers will have a medical procedure to obtain samples from the lungs (called a bronchoalveolar lavage) 14 days after their challenge infection to see if BCG remains in the airways. The results may indicate whether the vaccine is likely to be successful against Mycobacterium tuberculosis, and should be further tested in efficacy trials in TB endemic countries.
Volunteers are taking part in aerosol vaccine delivery trial at Oxford UniversityImage credit: University of Oxford
Professor Helen McShane, Professor of Vaccinology at Oxford's Jenner Institute, explains: 'The only vaccine we currently have against TB is the BCG, which unfortunately is not very effective against lung TB. We are looking at ways to deliver vaccine to the cells that will first to encounter TB bacteria, and this trial should give us important information about how our lungs respond to the early stages of infection. It will also be vitally important in the development of inhaled vaccines, which could be a much more effective way of protecting against many respiratory illnesses.'
This is a very exciting study and the first time an aerosol BCG-challenge model will be used to test a new TB vaccine. The study is funded by the National Institute of Health's National Institute of Allergy and Infectious Diseases as part of the IMPAc-TB consortium and is being conducted in collaboration with SCRI. The study is now open to recruitment and will start vaccinating participants in January 2025.
