Why centuries-old vaccines could become the next weapon against viruses

In the early days of the Covid-19 pandemic, when prevention seemed light years away, several scientists conducted trials to see if a tuberculosis vaccine was developed in the early days. 1900s can protect people by strengthening the immune system or not.

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 TB is common.

Years ago, scientists observed that this vaccine seemed to train the immune system to respond to a variety of infectious diseases, including viruses, bacteria, and parasites, and reduce infant mortality rate.

As new threats such as monkeypox and polio re-emerge and the coronavirus continues to evolve, the potential of older vaccines to provide a population-wide measure of protection against infectious diseases has emerged. gained new attention from scientists.

Now, the results of clinical trials conducted during the pandemic are approaching, 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 emerged. It was designed to see whether injecting multiple BCG may be beneficial for people with Type 1 diabetes, who are very susceptible to infections.

In January 2020, as the pandemic began, investigators began tracking Covid infections among 144 trial participants. They all have type 1 diabetes; Two-thirds had received at least three doses of BCG before the pandemic. The remaining one-third received multiple placebo injections.

Scientists are still assessing the long-term effects of the vaccine on type 1 diabetes. But they commissioned an independent team to look at Covid cases among participants for 15 months. , before any of them were vaccinated against Covid.

The results were dramatic: only one – or less than 1% – of the 96 people injected with BCG developed Covid, compared with 6 – or 12.5% ​​- of the 48 participants who received a mock injection.

Dr Denise Faustman, lead author of the study and director of the department of immunobiology at Massachusetts General Hospital, said: “Although the trial was relatively small, “the results were just as astounding as for the vaccine.” Moderna and Pfizer mRNA”.

People with Type 1 diabetes are especially susceptible to infections. Dr Faustman added: “We saw a significant reduction in bladder infections, fewer flu and colds, fewer respiratory infections and fewer sinus infections that diabetics get. “.

The vaccine “seems to be resetting the host’s immune response to become more alert, more responsive, not slower.”

Another trial of BCG in 300 older adults in Greece, all of whom had health problems such as heart or lung disease, showed that BCG vaccine reduces Covid-19 infections reduced by two thirds and reduced the rate of other respiratory infections.

According to research published in July in the journal Frontiers in Immunology, only two people who received the Covid-19 vaccine were hospitalized, compared with six who received a placebo.

“We have seen clear immune effects of BCG, and it is tempting to ask if we could use it – or other vaccines that produce a training effect on immunity – against a new, unknown and we don’t future pathogen, said Dr. Mihai Netea, co-author of the paper and professor at Radboud University Medical Center in the Netherlands.

He called the results of the type 1 diabetes trial “very strong,” but advised caution, noting that other trials have had disappointing results. One Dutch study of about 1,500 healthcare workers people vaccinated with BCG did not see a reduction in Covid infections and a South African study of 1,000 health care workers found no impact of BCG on the incidence or severity of Covid.

The results of the largest BCG test, an international study that followed more than 10,000 healthcare workers in Australia, the Netherlands, the UK, Spain and Brazil for a year, still being analyzed and expected for the next few months. The study also followed healthcare workers after they received the Covid vaccine to see if BCG improved their response.

“BCG is an area of ​​controversy – there are believers and disbelievers,” said lead investigator of that trial, Dr Nigel Curtis, professor of pediatric infectious diseases at the University of Melbourne in Australia and head of the Infectious Diseases Group of the Murdoch Children’s Research Institute. . (Dr. Curtis calls himself “an agnostic.”)

“No one is arguing that there are off-target effects, but how profound is that, and does it translate into clinical effects? And is it just for babies, who have more sensitive immune systems? These are very different questions,” says Dr. Curtis.

Several factors may account for the different findings. BCG consists of a live attenuated virus that has been cultured in laboratories around the world for decades, generating mutations that produce different strains.

Dr. Curtis said Dr. Faustman’s lab uses the Tokyo strain, which is considered particularly potent. His own studies used the Danish strain, which is the easiest to obtain. The number of doses can also affect immunity, as many vaccines require repeated injections to maximize protection.

Dr. Faustman said her work has shown that it takes time for a vaccine to take full effect. The type 1 diabetic in her study received several injections of BCG before the pandemic.

In any case, the scientists interested in BCG’s potential to provide universal, broad-spectrum protection against pathogens have repurposed their target. They are no longer interested in preventing Covid-19, because current vaccines are very effective.

Instead, they want to develop tools for use in the next pandemic, be it 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 of BCG and other vaccines that have demonstrated widespread protection.

“If we had known this from the very beginning of the Covid-19 pandemic, we could have achieved a great protective effect on the population in the first year of the pandemic.”

Chairman and co-founder Jaykumar Menon said the Open Source Pharma Foundation, a global nonprofit, is looking to develop new, affordable therapies in the areas of greatest need.

“Imagine if we could use existing vaccines to stop a pandemic – that would change world history,” Menon said, adding that BCG is not the only vaccine. have a broad spectrum of effects on the immune system.

Mr. Menon said.

Replace? “A widely available vaccine that works on innate immunity creates a strong moat to repel all species of comets,” he said.

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