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Mayo Clinic COVID-19 vaccine platform enters clinical trials

Researchers project that the single-cycle vector vaccine will produce a greater immune response and provide stronger protection against COVID-19 than current vaccine options.

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Dr. Michael Barry has been working on a single-cycle vector vaccine system for 13 years. This year, the technology entered clinical trials for the first time. (Courtesy of Mayo Clinic)

A new COVID-19 vaccine platform developed by Mayo Clinic researchers is entering phase one of clinical trials.

If it reaches the market, the single-cycle novel vaccine vector is expected to produce a greater immune response and a more effective barrier against COVID-19 than current vaccine options, according to Dr. Michael Barry, director of Mayo Clinic's Vector and Vaccine Engineering Laboratory.

For the needle-phobic, there is especially good news: the vaccine would likely be delivered through a nasal mist.


It’s a culmination of 13 years of work from Barry, who has previously used the vaccine platform to attempt to fight Ebola, HIV-1, influenza and Zika. This is the first time the system is entering a clinical trial.
“It’s exciting,” Barry said. “We worked very hard over the last year. When Mayo was pretty much shut down, we were not.”


The single-cycle system works like this: The protein that triggers an immune response against COVID-19 is delivered into a cell using a carrier vaccine, or vector. Barry's group uses an adenovirus vector. Once it arrives, the protein duplicates, amplifying the immune response against a potential threat.

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An explanation of the single-cycle vector system Dr. Michael Barry and his team developed as a way to create a more potent COVID-19 vaccine. (Courtesy of Mayo Clinic)

In a replication defective system, such as the one used in the Johnson & Johnson vaccine, the protein arrives in the cell and does not duplicate, producing a limited amount of antigen, the protein that triggers immune response.

Barry's system creates a more potent vaccine by allowing the antigen to multiply 100-fold.

“You can amplify the production of spike protein 100 times by letting the DNA replicate in the vector," he said. "And generally, in a vaccine setting, the more protein you can make, the stronger the protection you'll get.”

For the areas of the world experiencing vaccine shortages, this could unlock the potential to use fewer vaccines and inoculate more people.

The vaccine may be delivered nasally as a way to try to stop SARS-CoV-2 at its first point of entry to the body.


"Create a barrier at the earliest steps of an infection — if that infection starts with only one or a few SARS viruses present, it's a lot easier to stop it than after it amplifies and there's millions of them spreading to the lungs," Barry explained.

An adaptor placed on a syringe would nebulize the vaccine and spray it into the nose.

If the system is so effective, why aren’t more vaccine developers using it?

Barry said it all depends on the foundation developers have previously built upon. Many companies had years of work in replication defective viruses and couldn’t quickly pivot during the pandemic. His team had over a decade of work to build upon in single-cycle vectors. They just needed to prove the technology’s efficacy to key fundraisers.

"I think a lot of the Big Pharma guys are like, 'If you haven't done phase one, it's all kind of speculation,' " Barry said.

The technology was licensed to Tetherex Pharmaceuticals, a biopharma company in Oklahoma. After more than a decade of work and an especially strenuous year, Barry wished the technology could have stayed with Mayo Clinic, but he said funding got in the way of making that a reality.

"The platform will be used to target multiple infectious diseases, beginning with a Phase 1 clinical study investigating a vaccine for COVID-19. Dosing of the initial cohort of the Phase 1 study is underway in Australia," a news release from Tetherex stated.

Barry deferred to Tetherex to provide details on the clinical trial, but he said some participants were dosed with the vaccine last week. Tetherex did not respond to requests for comment.

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