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As COVID-19 was beginning its deadly trek around the globe last year, scientists at biopharmaceutical company VBI Vaccines were asking themselves a key question: Can a vaccine be created to deal with more than one kind of coronavirus?

The company, which is headquartered in Cambridge, Mass., and has its research operations in Ottawa, then began to develop a vaccine that would work against COVID-19 – in addition to SARS and MERS, the previous two coronavirus outbreaks, which began in 2002 and 2012 respectively. Last August, VBI’s Ottawa-based subsidiary, Variation Biotechnologies Inc., received a $56-million funding boost from the federal government to advance its program.

Now, after settling into a position well behind front-runners like Pfizer and Moderna, VBI’s approach is getting renewed attention – from media and investors alike – because of coronavirus variants that are springing up all over the world.

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“In a matter of only four weeks, we’ve seen these variants cause a huge instability in the whole vaccine rollout ... and in confidence about a return to normalcy,” said Jeff Baxter, VBI’s chief executive officer, in an interview with The Globe and Mail.

Can COVID-19 vaccines be combined? Do they work against variants? Pressing pandemic questions answered

Coronavirus tracker: How many COVID-19 cases are there in Canada and worldwide? The latest maps and charts

The company’s “multivalent” vaccine – the term for a vaccine that works against multiple viruses – will not be ready for human trials until later this year, Mr. Baxter said. In the meantime, VBI is planning to start trials by the end of March on a vaccine that is specifically tailored to COVID-19.

Both vaccines aim to deliver protection in the form of an enveloped virus-like particle. The particle consists of a protein core wrapped in a lipid envelope, from which copies of the coronavirus spike protein protrude. The design mimics the structure of the virus and is meant to trigger the immune system in a similar way.

In the case of the multivalent vaccine, the particle sports an array of different spike proteins that correspond to SARS, MERS and COVID-19. Studies with lab animals suggest it can generate an immune response against all three, as well as against a type of seasonal coronavirus that is not explicitly a target of the multivalent vaccine.

With new variants of COVID-19 emerging at a relatively rapid rate, Mr. Baxter said his company is considering whether the same strategy can be adapted to making a broad-spectrum vaccine that is effective against a range of coronaviruses – including some that have yet to surface in the human population.

“It’s a question of whether we can make the goal posts wider,” Mr. Baxter said.

Other vaccine-makers are similarly wondering how to cope with the fact that COVID-19 may be better at overcoming the immunological barriers erected against it than many scientists initially expected. That could lead to new formulations of existing vaccines to serve as booster doses, or to a continuing regimen of shots that might be needed if COVID-19 continues to shift and never completely disappears.

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“Right now almost all groups making vaccines – including us – are giving serious consideration to, or have already started to work on, variant or multivalent candidates,” said Brian Ward, co-director of McGill University’s vaccine study centre and medical officer at Medicago, the Quebec-based company that was the first in Canada to begin human trials of a COVID-19 vaccine.

Last month, Adagio Therapeutics, based in Waltham, Mass., reported a development that could point the way forward. A study published in the journal Science shows that an antibody developed by the company can lock onto a portion of the spike protein common to a family of coronaviruses, which includes the one that causes COVID-19. A vaccine that can stimulate the production of such an antibody might work as a “pan-vaccine” – in other words, not just killing a few birds with one stone, but an entire flock.

But there are reasons to be skeptical that either a multivalent or pan-vaccine can succeed in the near term, said virologist Arinjay Banerjee, who is setting up a new lab to study the diversity and origin of bat-borne coronaviruses at VIDO-Intervac, an infectious disease research institute based at the University of Saskatchewan.

“Variants appear in days and spread within weeks,” Dr. Banerjee noted, a timeline that outpaces even the most accelerated vaccine programs. And even if a pan-vaccine could anticipate variants that don’t yet exist, how would its efficacy be tested in a clinical trial?

In spite of these hurdles, the quest for a pan-coronavirus vaccine needs to start now, said Eric Topol, director of the Scripps Research Translational Institute in La Jolla, Calif. Last week, Dr. Topol and immunologist Dennis Burton wrote a commentary in the journal Nature calling for global investment to support the effort, in the range of $100-million to $200-million over a number of years.

Notwithstanding the new variants, Dr. Topol said, a coronavirus like COVID-19 is still far less adept at outwitting the human immune system than influenza or HIV, so it makes an ideal starting point for a pan-vaccine research program.

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“It kind of has a flashing sign on it saying, ‘You can crush me,’ ” he said. “The hope is that we can spawn a dedicated consortium of academics, companies and governments that get behind this.”

The large number of COVID-19 infections in some places makes it more likely for new variants of the virus to emerge. Science Reporter Ivan Semeniuk explains how vaccines may not be as effective against these new strains, making it a race to control and track the spread of variants before they become a dangerous new outbreak. The Globe and Mail

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