The aim is a broader type of immune response than can be achieved just by injecting into the muscles of the upper arm, including a more potent T cell response, researchers say
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Canadian scientists are set to start testing an inhaled COVID-19 vaccine in humans that targets not only the ever-mutating spike protein the pandemic virus uses to grab onto human cells, but two others that aren’t nearly so prone to mutations.
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Instead of being injected into the deltoid muscles in the arm, the McMaster University vaccine is delivered via tiny aerosol particles breathed deep into the lungs.
The vaccine is part of a second generation of COVID-19 vaccines and one of two Canadian-made formulas that hope to offer a more robust, and more stable immune response. Quebec-based Medicago Inc. reported Tuesday that its plant-based vaccine was 71 per cent effective against all variants of SARS-CoV-2 — except Omicron, which wasn’t circulating during the study — and 75 per cent effective against the globally dominant Delta variant, in a trial involving more than 24,000 adults across six countries.
Only three cases of severe cases occurred in the study, none in the vaccinated group.
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Medicago said it plans to “imminently” seek Health Canada approval. If approved, it would be the world’s first plant-produced vaccine to be used in humans.
The McMaster team’s vaccine is being trialed as a booster for people who have received two doses of an mRNA vaccine, such as Pfizer-BioNTech or Moderna. The original idea, early in the vaccine race, was to offer it as a standalone, “but as time has gone on, virtually everybody has now had the opportunity to get an mRNA vaccine,” said Fiona Smaill, a professor of pathology and molecular medicine at McMaster who is leading the human trial.
But with SARS-CoV-2 set to linger for months, perhaps years, and more booster doses likely to follow, it’s still important to test new vaccines that work in different ways, Smaill said.
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A potential godsend for the needle phobic, McMaster’s formula is administered through a jet nebulizer that generates a fine, misty solution, “with particles that are so tiny they’re breathed right down deep into the lung,” Smaill said. The delivery route is built on two decades of research on a tuberculosis vaccine led by McMaster professor Zhou Xing.
Once inside the lungs, the vaccine is designed to deliver a local “mucosal” response, right at the site where the virus enters the body. The aim is a broader type of immune response than can be achieved just by injecting into the muscles of the upper arm, including a more potent T cell response, the researchers said. T cells find and destroy infected cells.
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The vaccine uses strains of a weakened adenovirus, a family of viruses that cause the common cold. Two are being tested on 30 healthy volunteers — a vaccine using a human adenovirus, the other a chimpanzee adenovirus.
In addition to the spike protein that peppers the outside of SARS-CoV-2 and that the virus uses to slip inside human cells, the vaccine targets two cellular proteins inside the virus that it needs to grow and spread. “Mutations would be rarely seen in those proteins,” Smaill said.
“If you can generate that local immune response in the lung,” it may prove better to boost with an inhaled vaccine, she said. Canada has also shown that mixing vaccines can trigger a stronger response. “For a number of reasons, this has the promise of being a more effective way to boost,” Smaill said.
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Still, human trials are just beginning. Medicago has been submitting data to Health Canada as part of a rolling submission, and the federal government has a contract to purchase 20 million doses.
Medicago’s protein vaccine, which uses a GlaxoSmithKline adjuvant to enhance the immune response, uses a unique technology to produce virus-like particles designed to mimic the structure of the virus, but stripped of any harmful genetic information inside, making them non-infectious but able to trick the immune system into thinking it is “seeing” the virus.
“Our vaccine efficacy study has been performed in the period where it was dominated by variants, whereas other manufacturers performed their vaccine efficacy studies where only the original strain was circulating,” said Medicago’s Marc AndrĂ© D’Aoust, executive vice-president, innovation development and medical affairs.
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Medicago is also planning a study early in 2022 testing its vaccine as a booster.
Omicron has “supercharged ” the issue of boosters. If early anecdotal reports suggesting Omicron causes milder infections pan out, “I think we’re going to be okay,” Smaill said. But until more data are available, “we’re all guessing what’s actually going to happen.”
“We seem to be doing better, this time around, than we were a year ago. We’ve got vaccines. We’ve got an understanding of what the major risks are in terms of transmission. So we’ve made progress. How do we keep on, without ever going back? I think that’s really what I’m looking for.”
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2021-12-07 13:07:30Z
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