In mice, BCG-COVID vaccine works a treat, deepening the mystery of 100-year-old vaccine

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A vaccine based on a 100-year-old tuberculosis jab effectively prevents COVID-19 infection in mice – opening a unique path toward a new vaccine and deepening the intrigue around the older innoculation.

In a paper uploaded to BioRxiv earlier this month but not yet peer reviewed, a team of Sydney-based scientists showed mice immunised with their vaccine had almost no detectable virus or inflammation in their lungs after exposure to COVID-19.

Vaccine researcher Professor James Triccas in a lab at Sydney University.Credit:Nick Moir

“It compares very favourably with other licensed vaccines’ animal results,” said University of Sydney professor Jamie Triccas, head of the team working on the vaccine. “Clinically, it looks really good.”

The findings need to be taken with a grain of salt. Dozens of vaccines around the world are much closer to clinical production, and mice are not humans.

But the approach is globally unique: a shot of a cheap, widely available vaccine developed more than a century ago followed by a small chaser that could be quickly adjusted to target new COVID-19 variants.

The Bacille Calmette-Guerin tuberculosis vaccine is one of the world’s oldest jabs.

Derived by French scientists from the bacterium that gives cows tuberculosis, it was first given in Paris in 1921 and continues to be used around the world (Australia limits its use because tuberculosis is not prevalent here).

But it turns out BCG offers much wider protection against a range of other respiratory viruses children face, trials have repeatedly shown – a finding that has long puzzled scientists.

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But in recent years, researchers have discovered an ancient property of the immune system: ‘trained immunity’. Much like hitting the gym builds strong muscles, it seems exposure to certain diseases can change the genes expressed by immune cells, potentially making them more powerful. Think of BCG as the personal trainer.

There are tantalising hints in the data – countries that routinely offer the BCG vaccine to children have lower overall COVID-19 infection numbers.

A large international trial led by the Parkville-based Murdoch Children’s Research Institute is now testing whether the BCG vaccine alone can provide some measure of protection against COVID-19.

The immune-boosting properties of the BCG vaccine prompted Professor Triccas to ponder: could BCG form the backbone of a whole new protein-based COVID-19 vaccine?

“We don’t want to overlook protein vaccines. They have a long track record, they tend to be quite effective, they don’t have complicated storage requirements. And you can develop a lot of doses quite quickly,” said Professor Triccas.

His vaccine combines the BCG shot and a sample of SARS-CoV-2’s spike protein.

BCG acts as the vaccine’s adjuvant, telling the immune system to develop antibodies against the spike protein – theoretically providing lasting immunity against COVID-19.

The vaccine could come in a one or two-jab version, where a person might be given a standard BCG vaccine and then a small booster containing the spike protein.

Millions of doses of BCG are already manufactured each year; the small booster could be quickly and cheaply manufactured, and easily tweaked to cover new variants of the virus.

“The results showing the generation of a neutralising immune response after only a single dose of BCG-CoVac are impressive. Two doses are required for almost all of the available COVID vaccines,” said associate professor Keith Chappell, a member of the vaccine development team behind the University of Queensland’s aborted COVID jab.

Professor Chappell was not involved in the research.

If that approach can be proven in human trials, developing countries that offer the BCG vaccine could simply add a small extra dose to provide protection against COVID-19.

To progress any further, the team now needs to raise money for human clinical trials.

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