Led by the Murdoch Children’s Research Institute (MCRI) in Melbourne, the BRACE trial started in Australia on March 27. A grant of more than $10m from the Bill and Melinda Gates Foundation has allowed its global expansion with study centres added in the Netherlands, Spain and Brazil. This week the University of Exeter, which is leading the UK arm of the trial, announced it would start recruitment for UK participants.
The trial aims to recruit 10,000 healthcare workers across the world. The results of the trial will help show whether the BCG vaccine could be used as an early intervention measure to protect healthcare workers and high-risk groups: both in the COVID-19 pandemic and future novel viral outbreaks.
BCG: increasing innate immunity?
The Bacillus Calmette-Guerin (BCG) vaccine protects against tuberculosis and is given to more than 130 million babies worldwide each year. In the UK it is no longer given routinely (it was stopped in 2005 because of low rates of tuberculosis in the general population) although it is sometimes given to adults who are at risk of tuberculosis through their work.
While the BCG vaccine is designed to vaccinate against tuberculosis, it also boosts the immune system to fight against other infections. Previous studies suggest the vaccine could reduce susceptibility to a range of infections caused by viruses - including those similar to the novel coronavirus causing COVID-19.
Why is the BCG vaccine of interest?
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a single-stranded positive-sense RNA virus, and the BCG vaccine has been shown to reduce the severity of infections by other viruses with that structure in controlled trials. For example, a 2018 study suggested the BCG vaccine reduced yellow fever vaccine viraemia by 71% in volunteers in the Netherlands, while two mice studies showed it reduces the severity of mengovirus (encephalomyocarditis virus) infection.
However, the WHO’s current recommendation is that the BCG vaccine is used for COVID-19 only in trials such as this one. This is because the BCG vaccine is already in short supply and needed for protecting children against tuberculosis in high-risk areas. Secondly, its effectiveness against COVID-19 remains unknown.
Scientists also highlight that a BCG vaccine given in childhood decades ago – as was the case in the UK – is unlikely to work against COVID-19 today.
The BRACE trial is focusing on healthcare workers, who are at greater risk of contracting COVID-19 pandemic, in the hope it could help boost innate immunity against subsequent infections: thus buying time in the race to develop an effective and safe vaccine against COVID-19.
In the UK, the trial is initially recruiting 1,000 care and health care workers in the South West of England, who can attend clinics in Exeter. Researchers are targeting these professionals because they work in fields with high exposure to COVID-19.
The trial is specifically looking at whether the BCG vaccine reduces coronavirus infection or COVID-19 symptom severity. Participants will be asked to complete a daily symptom diary via an app, be tested for COVID-19 whenever they have symptoms, complete regular questionnaires and provide blood samples. These samples will allow scientists to understand how blood cells respond differently to exposure to COVID-19 and other viruses, with and without the BCG vaccine.
The trial plans to expand to other sites across the UK following the intial launch in Exeter.