Oxford marks World Tuberculosis Day as vaccine trials continue

In 2023, Tuberculosis (TB) caused more deaths worldwide than any other infectious disease. It is caused by the bacterium Mycobacterium tuberculosis, and although largely unheard of in the developed world by the late 20th century, cases have been rising globally in recent years and it continues to place an enormous social and economic burden on much of the developing world.

Although often thought of as a lung disease, TB can infect other parts of the body, including the brain and the spine.

Currently the only licensed vaccine against TB is Bacillus Calmette-Guérin (BCG), an old vaccine which has been given to millions of people 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.  The vaccine is 70-80% effective against the most severe forms of TB, such as TB meningitis, but it is much less effective in preventing the form of TB that affects the lungs.

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 burdens of TB disease. An effective vaccine is urgently needed to reduce the spread of infection, prevent progression to active disease, and save lives.

Professor Helen McShane, Professor of Vaccinology at Oxford's Jenner Institute, explains: 'Tuberculosis, in the 21st century, still kills more people than any other infectious disease. We urgently need to develop effective vaccines, as the most cost-effective way to control this epidemic.

'It has been more than a century since the BCG vaccine was developed, and the increasing rise of antimicrobial resistance globally makes it more important than ever before to discover new ways to protect against this terrible disease before we run out of drugs to treat those suffering with it.

'The impact of TB on many developing nations cannot be understated. Its spread is exacerbated by poor access to healthcare, nutrition and sanitation, and it itself compounds these conditions and places a growing economic social burden on the poorest in society.'

Researchers from Oxford’s Jenner Institute have been working on several vaccines to protect against TB for many years. TB046 is a study comparing the effectiveness of giving the BCG vaccine via the traditional skin injection to giving it as an aerosol spray which is inhaled into the lungs. As the natural route of infection with tuberculosis is through inhalation of droplets into the lungs, this study is hoped to be better at stimulating the immune system.

Jenner Institute researchers have also begun a pioneering new human challenge model to test new TB vaccines, called TB045. A challenge model deliberately exposes participants to a pathogen in order to test the effectiveness of the vaccine they have received beforehand, and have been used successfully to test vaccines for diseases such as malaria. TB is a far too dangerous an organism to risk exposing healthy people to, so this new trial will use the BCG vaccine itself in place of TB because it behaves similarly but is safe to use.

In this study, which is being run in partnership with the Coler Lab at Seattle Children’s Research Institute (SCRI), 24 volunteers will receive a 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 whether the ID93+GLA-SE vaccine protects against aerosol mycobacterial challenge. 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. Due to the number of different research specialists across Oxford who are involved in such complex trials, these take place at Oxford's EMCRF - a Clinical Research Facility providing a resource for early phase, experimental research across the Medical Sciences Division.

This is the first time an aerosol BCG-challenge model will be used to test a new TB vaccine, and will be important in developing a way to test future TB vaccines. 

There is a long way to go to turn the tide on this disease that has plagued humanity since the dawn of civilisation, but international collaboration and competition will be essential in making that happen.