In the early days of the Covid-19 pandemic, when prevention seemed light years away, several scientists launched trials to see if a tuberculosis vaccine developed in the early 1900s could protect people by boosting the immune system.
The Bacillus-Calmette-Guerin vaccine has long been known to have broad effects on the immune system and is still given to infants in developing countries and in countries where tuberculosis is common.
Scientists determined many years ago that the vaccine appears to train the immune system to respond to a variety of infectious diseases, including viruses, bacteria and parasites, and reduces infant mortality.
As new threats such as monkey pox and polio resurface and the coronavirus continues to evolve, the potential of the ancient vaccine to provide some degree of universal protection against infectious diseases has attracted renewed interest among scientists.
Now the results of clinical trials conducted during the pandemic are coming in, and the findings, while mixed, are encouraging.
The latest results, published Monday in Cell Medicine Reports, come from a trial that was started before Covid-19 showed up. It was designed to see if multiple BCG injections could benefit people with type 1 diabetes, who are very prone to infections.
In January 2020, as the pandemic began, the researchers began detecting Covid infections among the 144 participants in the study. They all had type 1 diabetes; two-thirds had received at least three doses of BCG before the pandemic. The remaining one-third had received multiple placebo injections.
The scientists are still evaluating the vaccine’s long-term effects on type 1 diabetes itself. But they instructed an independent group to look at Covid infections among the participants for 15 months before any of them received Covid vaccines.
The results were dramatic: Only one — or less than 1 percent — of 96 people who received the BCG doses developed Covid, compared with six — or 12.5 percent — of 48 participants who received dummy-doses. received injections.
Although the trial was relatively small, “the results are just as dramatic as for the mRNA vaccines from Moderna and Pfizer,” says Dr. Denise Faustman, lead author of the study and director of immunobiology at Massachusetts General Hospital.
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People with type 1 diabetes are especially prone to infections. “We saw a great decrease in bladder infections, less flu and fewer colds, fewer respiratory infections and fewer sinus infections that diabetics get a lot of,” added Dr. Faustman to it.
The vaccine “seems to reset the host’s immune response to be more alert, more prepared, not so slow.”
Another study of BCG in 300 older Greek adults, all of whom had health problems such as heart or lung disease, found that the BCG vaccine reduced Covid-19 infections by two-thirds and also lowered the number of other respiratory infections.
Only two individuals who received the vaccine were hospitalized with Covid-19, compared with six who received the placebo injections, according to the study published in Frontiers in Immunology in July.
“We have seen clear immunological effects of BCG, and it is tempting to ask whether we could use it – or other vaccines that induce training effects on immunity – against a new pathogen emerging in the future that is unknown and that we have don’t have a vaccine for that,” said Dr. Mihai Netea, co-lead author of the paper and a professor at the Radboud University Medical Center in the Netherlands.
He called the results of the type 1 diabetes study “very strong,” but urged caution, noting that other studies had disappointing results. A Dutch study of approximately 1,500 health professionals vaccinated with BCG found no reduction in Covid infections, and a South African study of 1,000 health professionals found no effect of BCG on the incidence or severity of Covid.
The results of BCG’s largest study, an international study that followed more than 10,000 health professionals in Australia, the Netherlands, the UK, Spain and Brazil, are still being analyzed and are expected in the coming months. The study also followed health professionals after they received Covid vaccines to see if BCG improved their responses.
“BCG is a controversial area — there are believers and non-believers,” said the lead researcher of that trial, Dr. Nigel Curtis, a professor of childhood infectious diseases at the University of Melbourne in Australia and leader of the Infectious Diseases Group at the Murdoch Children’s Research Institute. . (Dr. Curtis calls himself “an agnostic.”)
“Nobody is claiming there are off-target effects, but how profound is that and does it translate to a clinical effect? And is it limited to newborns, whose immune systems are more susceptible? These are very different questions,” said Dr. Curtis. .
A number of factors could explain the divergent findings. BCG is composed of a live attenuated virus that has been grown in labs around the world for decades and introduces mutations that cause different strains.
The lab of Dr. Faustman uses the Tokyo strain, which is considered particularly potent, said Dr. curtis. His own studies used the Denmark strain, which is the easiest to obtain. The number of doses can also have an effect on immunity, as many vaccines require repeated vaccinations to maximize protection.
dr. Faustman said her work has shown that it takes time for the vaccine to have its maximum effect. Type 1 diabetes patients in her study had received several BCG injections before the pandemic.
In any case, scientists interested in BCG’s potential to provide universal, broad-spectrum protection against pathogens have rearranged their objectives. They are no longer looking at preventing Covid-19 as current vaccines are very effective.
Instead, they want to develop tools for use in the next pandemic, which could be another coronavirus, a deadly new strain of flu, or an unknown pathogen.
“It’s more for the future,” said Dr. Netea, who has called for large clinical trials to be conducted on BCG and other vaccines that have demonstrated broad protective effects.
“If we had known this at the beginning of the Covid-19 pandemic, we could have achieved a major protective effect on the population in the first year of the pandemic.”
The Open Source Pharma Foundation, a global nonprofit that aims to develop affordable new therapies in the areas of greatest need, is interested in reusing non-proprietary vaccines for use in current and future pandemics, said its chairman and co-founder Jaykumar Menon.
“Imagine if we could use existing vaccines to curb pandemics – that would change world history,” said Mr Menon, adding that BCG is not the only vaccine with broad effects on the immune system.
“These narrow, very specific vaccines, like the Pfizer or Moderna mRNA vaccines, are placed very closely on the spike protein of the virus that causes Covid-19, but if that protein mutates – which it does – you lose the efficacy,” Menon said.
The alternative? “A broad universal vaccine that works on innate immunity sets up this fortified moat that repels all newcomers,” he said.