Trials begin on Omicron-specific booster vaccine developed by Adelaide researchers

A new vaccine targeting the Omicron COVID-19 variant has been designed by Australian researchers at the University of Adelaide and is now commencing human trials.

Manufactured in South Australia at the FDA-approved BioCina facility in Adelaide, the DNA vaccine is one of the very few vaccines worldwide specifically targeting the highly transmissible Omicron variant.

This type of vaccine is especially valuable because it could easily be adapted, and manufactured more quickly than mRNA vaccines, in response to new COVID-19 variants as they emerge.

The researchers are calling on volunteers to participate in the trial, where the vaccine will be delivered painlessly under the skin using a needle-free device.

Why a booster for Omicron specifically?

Unfortunately, we’re stuck living with COVID-19 indefinitely.

So it’s important to evaluate booster vaccines that target specific variants, because the virus’ genome will only continue to mutate – particularly in countries with low vaccination rates and high rates of uncontrolled transmission.

“We can only speculate that the Omicron vaccine will be more effective against an Omicron variant,” says Professor Eric Gowans, a senior research fellow from the University’s Adelaide Medical School.

“But one would predict that that would be the case, because vaccines against the original strain of virus are less effective against variants.”

Gowans is co-leading the trial alongside Associate Professor Branka Grubor-Bauk, head of Viral Immunology at the Adelaide Medical School.

The Viral Immunology Group have been working on the SARS-Cov-2 vaccine for about 18 months, first making a DNA vaccine against the original strain, and then against the Delta strain.

“When the new Omicron variant came along, we really took a punt that this was likely to be a major new strain and so we actually decided to make the Omicron vaccine,” explains Gowans. “When the genetic sequence of the Omicron variant was published in late November last year, we made the changes and we actually had the Omicron vaccine in animals on the 28th of December.

What’s the difference between DNA and mRNA vaccines?

Not a whole lot it turns out.

Both DNA and mRNA vaccines are made using plasmids (circular DNA) containing a DNA sequence that encodes for the viral protein that you want the immune system to recognise.

To produce a protein from a DNA sequence it first needs to be transcribed into mRNA, which is then translated by a protein (ribosome) in your cells.

“Although the processes are very similar, we can get the DNA vaccine into the patient quicker than we can an mRNA vaccine because the mRNA vaccine has to go through an additional process of manufacturing,” says Gowans.

In mRNA vaccines, the DNA plasmid is used to make mRNA in a manufacturing facility like BioCina, which is then incorporated into a vaccine that is injected into your body.

But in DNA vaccines this intermediary step isn’t necessary, because by administering the DNA plasmid directly to your cells, the mRNA is made inside the body instead.

This vaccine targets a specific region of the spike protein

So, which viral protein is being made by your cells when you’re given this DNA vaccine?

The DNA codes for a region of the spike protein – found on the surface of the virus – that’s called the receptor binding domain.

This is the region on the spike protein that directly recognises and binds to the ACE2 receptor on the surface of human cells (mainly in the lung, intestine, heart and kidney) and allows it to invade the cell.

An antibody made by the immune system that recognises and binds to this region is called a neutralising antibody, because it can stop the virus from infecting you by disrupting how the virus enters cells.

According to Gowans, the Omicron variant has a greater number of mutations than any other variant, including delta and an alpha, in this receptor-binding domain.

“The antibody generated by the original vaccine doesn’t bind effectively to the variants’ spike protein,” he says.

“We have cut out regions in the spike which are extraneous to that so that we use the receptor binding domain alone, and we expect that that will be a much more effective vaccine.”

And it won’t be delivered via a needle, but instead using a device from a company called Pharmajet, in the US. The device uses a high velocity fluid delivery system to deliver a spray of vaccine underneath the skin, where there is a much higher proportion of immune cells than in the muscles.

“An intradermal delivery is much more efficient and effective than intramuscular,” adds Gowans.

Local manufacturing for future supplies to Australia and overseas

Australia has had difficulties in the past with sourcing COVID-19 vaccines quickly from overseas, but manufacturing vaccines locally would cut out this potential supply problem.

DNA vaccines also have enormous advantages in terms of distribution and storage because they are stable at higher temperatures than mRNA vaccines.

“We of course we can’t test this vaccine specifically, but we know from other DNA vaccines that they have a shelf life of around five years. And this vaccine can be shipped and stored at 4°C, probably room temperature, if necessary,” explains Gowans.

This makes it much easier to transport, not only to people around Australia but to developing countries around the world, compared to the challenges of shipping an mRNA vaccine stored at -20°C or -70°C.

The Omicron vaccine is being trialled at the Royal Adelaide Hospital, in partnership with PARC Clinical Services and SA Pathology, with research undertaken at the Basil Hetzel Institute for Translational Health Research at The Queen Elizabeth Hospital precinct.

The research has been funded by the Hospital Research Foundation Group.

Volunteers who are over the age of 18, triple vaccinated more than three months ago, and have not had COVID-19 can express their interest here.

Participants must have received either the Pfizer or AstraZeneca vaccines previously, as Moderna provokes a slightly different immune response, and they need to keep things consistent.

According to Gowans, the team are expecting to monitor participants’ immune responses 2-3 times for about three months after receiving their dose.

---

Interested in having science explained? Listen to our new podcast.