How exactly can scientists adapt a COVID vaccine for Omicron?

If omicron variant of coronavirus sufficiently different from the original variant, it is possible that existing vaccines will no longer be as effective as they once were. If so, it’s likely companies will need to update their vaccines to better fight omicrons. Deborah Fuller is a microbiologist who has studied mRNA and DNA vaccines for more than two decades. Here, she explains why vaccines may need to be updated and what that process will look like.

Why do vaccines need to be updated?

It’s essentially a question of whether a virus has changed enough that the antibodies produced by the original vaccine can no longer recognize and fight the new mutated variant.

Coronavirus uses spike proteins to attach to ACE-2 receptors on the surface of human cells and infect them. All COVID-19 mRNA vaccines work by giving instructions in the form of mRNA directing cells to make a harmless version of the mutant protein. Then, this spike protein causes the human body to make antibodies. If a person is subsequently exposed to the coronavirus, these antibodies bind to the mutant protein of the coronavirus and thus interfere with the person’s ability to infect cells.

The omicron variant contains a new mutation for its mutant protein. These changes could disrupt the ability of some – but perhaps not all – of the antibodies produced by current vaccines to bind to the mutant protein. If that happens, the vaccine may be less effective at preventing people from getting and transmitting the omicron variant.

How would a new vaccine be different?

Existing mRNA vaccines, such as those made by Moderna or Pfizer, code for a mutated protein from the original coronavirus strain. In new or updated vaccines, the mRNA instructions will code for the omicron spike protein.

By swapping the genetic code of the original mutant protein for the genetic code from this new variant, a new vaccine will generate antibodies that more effectively bind to the omicron virus and prevent it from spreading infect cells.

People who have been immunized or previously exposed to COVID-19 may need only a single booster dose of the new vaccine to be protected not only from the new strain but also other strains that may still be present. onion. If omicron emerges as the dominant line to delta, then unvaccinated individuals will only need to receive 2-3 doses of the updated vaccine. If both delta and omicron were in circulation, people would likely receive a combination of current and up-to-date vaccines.

NIH

How do scientists update a vaccine?

To create an updated mRNA vaccine, you need two components: the genetic sequence of the mutated protein from a new variant of interest, and a DNA template that will be used to generate the mRNA.

In most organisms, DNA provides the instructions for making mRNA. Since the researchers have published the genetic code for the omicron mutant protein, all that remains is to create a DNA template for the mutant protein that will be used to produce the mRNA portion of the new vaccine.

To do this, the researchers mix DNA samples with synthetic enzymes and the four molecular building blocks that make up mRNA — G, A, U, and C for short. The enzymes then build a copy. copy the mRNA of a DNA template, a process known as transcription. Using this process, it takes only a few minutes to produce a batch of vaccine mRNA. The researchers then placed copies of the mRNA in fatty nanoparticles that protected the guides until they were safely delivered into the cells in your arm.

How long until a new vaccine could be ready?

It takes just three days to generate the DNA sample needed to make a new mRNA vaccine. It will then take about a week to produce enough doses of the mRNA vaccine for laboratory testing, and another six weeks to perform preclinical tests on human cells in vitro to ensure a vaccine. New works as usual.

So, within 52 days, scientists can have an up-to-date mRNA vaccine ready to go into production and start producing doses for human clinical trials. That trial will likely take at least a few more weeks out of a total of about 100 days to update and test a new vaccine.

While that trial is happening, manufacturers can begin to move their current process into making a new vaccine. Ideally, once the clinical trial is complete — and if a vaccine is approved or approved — a company can begin rolling out new doses of the vaccine immediately.

Mike Blake / Reuters

Does an updated vaccine need a full clinical trial?

It is not clear how much clinical data is needed for FDA approval or authorization for an updated COVID-19 vaccine. However, all the components will be the same in a new vaccine. The only difference would be that a few lines of genetic code can slightly change the shape of the mutant protein. From a safety perspective, the updated vaccine is essentially the same as the tested vaccines. Because of these similarities, clinical trials may not be as extensive as what is needed for a first-generation COVID-19 vaccine.

At a minimum, clinical trials of the updated vaccine will likely require safety testing and confirmation that the updated vaccine produces antibody levels equal to the response of the original vaccine to parent, beta and delta strains. If these were the only requirements, researchers would only enroll hundreds – not tens of thousands of people – to obtain the necessary clinical data.

It is important to note that if vaccine manufacturers decide to update their vaccines for the omicron variant, this will not be the first time they have made this type of change.

An earlier variant, B.1.351, appeared in October 2020 and is resistant enough to current vaccines to warrant updating them. Manufacturers quickly responded to the potential threat by developing an updated mRNA vaccine to accommodate this variant and conducting clinical trials to test the new vaccine. Fortunately, this variation did not become the dominant one. But if it does, vaccine manufacturers are poised to roll out an updated vaccine.

If it turns out that the omicron — or any future variant, for that matter — warrants a new vaccine, the companies have already completed costume rehearsals and are ready to face the challenge. .

Deborah Fuller is a professor of microbiology at the University of Washington School of Medicine