A vaccine created more than a century ago offers new hope against pathogens

At the beginning of the Covid-19 pandemic, when prevention seemed light-years away, several scientists began trials to see if a TB vaccine developed in the early 20th century could protect people by strengthening the immune system.

It has been known for years that the Bacillus Calmette-Guerin (BCG) vaccine has broad effects on the immune system. It is still given to babies in the developing world and in countries with a prevalence of tuberculosis.

Scientists observed many years ago that the vaccine appears to train the immune system to react to a range of infectious diseases, including viruses, bacteria and parasites, and reduce infant mortality.

With the resurgence of new threats like monkeypox and polio, and with the coronavirus continuing to evolve, the potential of the old vaccine to provide a universal measure of protection against infectious disease has attracted renewed interest among scientists.

Now the results of clinical trials carried out during the pandemic are starting to come in, and the conclusions, although uneven, are encouraging.

Published Monday in Cell Medicine Reports, the latest results are from a trial that began before Covid-19 emerged. The trial was designed to see whether multiple injections of BCG could benefit people with type 1 diabetes, who are highly susceptible to infections.

In January 2020, at the start of the pandemic, researchers began tracking Covid infections among the 144 participants in the trial. All had type 1 diabetes, and two-thirds of them had received at least three doses of BCG before the pandemic. The remaining third had received multiple injections of placebo.

Scientists are still evaluating the vaccine’s long-term effects on type 1 diabetes itself. But they hired an independent group to analyze Covid infections among the participants for 15 months, before any of them had had Covid vaccines.

The results were striking: only one (i.e. just over 1%) of the 96 people who had received the BCG doses developed Covid-19, versus six (or 12.5%) of the 48 participants who had taken placebo injections. .

Although the trial was relatively small, “the results are as impressive as those of the Moderna and Pfizer mRNA vaccines,” said Dr. Denise Faustman, the study’s lead author and director of immunobiology at Massachusetts General Hospital.

People with type 1 diabetes are especially prone to infections. “We’ve seen a major reduction in urinary tract infections, less flu and colds, fewer respiratory tract infections and fewer sinus infections, which is something that affects a lot of diabetics,” Faustman added.

According to her, the vaccine “seems to be resetting the host’s immune response to make it more alert, more prepared, less lazy.”

Another BCG trial was done on 300 elderly Greek adults, all with health conditions such as heart or lung disease. The BCG vaccine was seen to reduce Covid infections by two-thirds and also lower rates 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 July in Frontiers in Immunology.

“We’ve seen clear immunological effects of BCG, and it’s tempting to ask whether we can use this vaccine — or others that induce immunity-training effects — against a new pathogen that may emerge in the future, that is unknown and for which we don’t have a vaccine.” , said Dr. Mihai Netea, lead co-author of the paper and professor at Radboud University Medical Center in the Netherlands.

He described the results of the trial in people with type 1 diabetes as “very strong,” but urged caution, noting that other trials had disappointing results. A Dutch study of 1,500 healthcare workers vaccinated with BCG did not find a reduction in Covid infections, and a South African study of 1,000 healthcare workers did not identify any impact of BCG on the incidence or severity of Covid.

Results from BCG’s largest clinical trial — an international study that followed more than 10,000 healthcare professionals from Australia, the Netherlands, the UK, Spain and Brazil for a year — are still being analyzed and are expected to arrive in the coming months. The study also followed healthcare workers after they received Covid vaccines to see if BCG improved their response.

“BCG is a controversial issue — there are believers and non-believers,” said lead researcher of that trial, Nigel Curtis, professor of pediatric infectious diseases at the University of Melbourne in Australia and leader of the Infectious Diseases Group at Murdoch Children’s Research. Institute. He describes himself as “agnostic”.

“Nobody disputes that there are effects that are not intended, but how profound is that, and does it translate into a clinical effect? ​​And is it limited to newborns, whose immune systems are much more susceptible? These are very different questions. “, Curtis said.

Several factors may explain the disparate conclusions. BCG is composed of a live attenuated bacterium that has been cultivated for decades in laboratories around the world, introducing mutations that give rise to different strains.

Faustman’s lab uses the Tokyo strain, which is considered especially potent, Curtis said. His own studies used the strain from Denmark, the easiest to obtain. The number of doses can also have an effect on immunity, as many vaccines require repeated inoculations to maximize protection.

Faustman said his work showed that it takes time for the vaccine to reach its maximum effect. The type 1 diabetes patients in their study received multiple doses of BCG prior to the Covid pandemic.

Either way, scientists interested in BCG’s potential to provide universal, broad-spectrum protection against pathogens have already reformulated their goals. They are no longer aiming to prevent Covid, as current vaccines are very effective.

Instead, they want to develop tools for use in the next pandemic, which could be another coronavirus, a new, lethal strain of influenza, or an unknown virus.

“It’s more for the future,” said Netea, who called for large clinical trials of BCG and other vaccines that have already been shown to have broad protective effects. “If we had known this at the beginning of the Covid pandemic, we could have had a great protective effect on the population in the first year of the pandemic.”

The Open Source Pharma Foundation, a global not-for-profit organization working to develop new, affordable therapies in areas where they are most needed, is interested in repurposing patent-expired vaccines for use in current and future pandemics. The information is from the president and co-founder of the entity, Jaykumar Menon.

“Imagine if we could use existing vaccines to limit pandemics — that would change human history,” said Menon, noting that BCG is not the only vaccine that has broad effects on the immune system.

“These very specific vaccines, like the mRNA vaccines from Pfizer or Moderna, lodge very heavily in the spike protein of the virus that causes Covid, but if that protein mutates — and it does — you lose effectiveness,” Menon said. .

The alternative? “A universal and broad vaccine that boosts innate immunity and builds a fortified moat that repels all attackers,” he said.

_{Translation by Clara Allain}