How Scientists Can Update Coronavirus Vaccines for Omicron

Some vaccines use mRNA to make copies of the triangular red spike proteins to induce immunity.

If the ommicron variant of the coronavirus is sufficiently different from the original variant, existing vaccines may not be as effective as they were. If so, it’s likely companies will need to update their vaccines to better fight ommicrons. Deborah Fuller is a microbiologist who has studied mRNA and DNA vaccines for more than two decades. Here she explains why vaccines may need updating and what that process would look like.

1. Why Vaccines May Need to Be Updated?

Basically, what matters is whether a virus has changed enough that antibodies made by the original vaccine can no longer recognize and ward off the new mutated variant.

Coronaviruses use spike proteins to attach to and infect ACE-2 receptors on the surface of human cells. All mRNA COVID-19 vaccines work by providing instructions in the form of mRNA that direct cells to make a harmless version of the spike protein. This spike protein then prompts the human body to produce antibodies. Then, if a person is ever exposed to the coronavirus, these antibodies bind to the coronavirus spike protein and thus interfere with the ability to infect that person’s cells.

The ommicron variant contains a new pattern of mutations in its spike protein. These changes may interfere with the ability of some – but probably not all – antibodies induced by current vaccines to bind to the spike protein. If that happens, the vaccines may be less effective at preventing people from becoming infected with and transmitting the omicron variant.

2. How Would a New Vaccine Be Different?

Existing mRNA vaccines, such as those made by Moderna or Pfizer, encode a spike protein from the original strain of the coronavirus. In a new or updated vaccine, the mRNA instructions would encode the ommicron spike protein.

By replacing the genetic code of the original spike protein with that of this new variant, a new vaccine would induce antibodies that bind the omicron virus more effectively and prevent it from infecting cells.

People who have already been vaccinated or previously exposed to COVID-19 will likely only need a single booster dose of a new vaccine to be protected not only against the new strain, but also against other strains that may still be in circulation. If omicron emerges as the dominant strain over delta, then those not vaccinated only need to get 2-3 doses of the updated vaccine. If delta and omicron were both in circulation, people would likely receive a combination of the current and updated vaccines.

By changing the mRNA sequence in a vaccine, researchers can change the antibody-producing protein it encodes to better match new variants.

3. How do scientists update a vaccine?

To make an updated mRNA vaccine, you need two ingredients: the genetic sequence of the spike protein of a new variant of concern and a DNA template that would be used to build the mRNA.

In most organisms, DNA provides the instructions for making mRNA. Since researchers have already published the genetic code for the omicron spike protein, all you need to do is create a DNA template for the spike protein that would be used to produce the mRNA portion of new vaccines.

To do this, researchers mix DNA templates with synthetic enzymes and four molecular building blocks that make mRNA — G, A, U, and C for short. The enzymes then build an mRNA copy of the DNA template, a process called transcription. . With this process, it only takes a few minutes to produce a batch of vaccine mRNA. Researchers then place the mRNA transcripts in fatty nanoparticles that protect the instructions until they’re safely delivered to cells in your arm.

4. How long does it take for a new vaccine to be ready?

It only takes three days to generate the DNA template needed to make a new mRNA vaccine. After that, it would take about a week to produce enough doses of the mRNA vaccine for lab testing and another six weeks to run the preclinical tests on human cells in test tubes to make sure a new vaccine works. as it should be.

So within 52 days, scientists could have an updated mRNA vaccine ready to plug into the manufacturing process and begin producing doses for a human clinical trial. That trial would likely need at least a few more weeks for a total of about 100 days to update and test a new vaccine.

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

Both Moderna and Pfizer have made statements saying they could have the vaccines ready for trials in less than 100 days.

5. Does an Updated Vaccine Need Full Clinical Trials?

It is currently unclear how much clinical data is needed to gain FDA approval or authorization for an updated COVID-19 vaccine. However, in a new vaccine, all the ingredients would be the same. The only difference would be a few lines of genetic code that would slightly change the shape of the spike protein. From a safety point of view, an updated vaccine is essentially identical to the vaccines already tested. Because of these similarities, clinical trials may not need to be as extensive as what was required for the first generation of COVID-19 vaccines.

At the very least, clinical trials for updated vaccines would likely require safety testing and confirmation that an updated vaccine induces antibody levels comparable to the response of the original vaccine against the original, beta and delta strains. If these were the only requirements, researchers would enroll only hundreds – not tens of thousands – of people to obtain the necessary clinical data.

One important thing to note is that if vaccine manufacturers decide to update their vaccines for the omicron variant, it wouldn’t be the first time they’ve made these kinds of changes.

An earlier variant, B.1.351, appeared in October 2020 and was sufficiently resistant to the then-current vaccines to warrant an update. Manufacturers quickly responded to the potential threat by developing an updated mRNA vaccine to match this variant and conducting clinical trials to test the new vaccine. Fortunately, this variant has not become the dominant variant. But if it had, vaccine manufacturers would have been ready to roll out an updated vaccine.

If it turns out that ommicron — or any future variant — warrants a new vaccine, companies have already completed the dress rehearsals and are ready to take on the challenge.

Written by Deborah Fuller, Professor of Microbiology, School of Medicine, University of Washington.

This article was first published in The Conversation.