How can scientists update the coronavirus vaccines for omicron? | Kiowa County Press

Some vaccines use mRNA to make copies of triangular red tip proteins to induce immunity. Juan Gaertner / Science Photo Library via Getty Images

Deborah Fuller, Washington University

If the omicron variant of the coronavirus is different enough from the original variant, the existing vaccines may not be as effective as they used to be. If so, it’s likely that companies will need to update their vaccines to better tackle omicron. Deborah Fuller is a microbiologist who has studied mRNA and DNA vaccines for over two decades. Here she explains why vaccines might need to be updated and what that process would look like.

1. Why do vaccines need to be updated?

Basically, it’s a question of whether a virus has changed enough that the antibodies created by the original vaccine are no longer able to recognize and repel the new mutated variant.

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

The omicron variant contains a new pattern of mutations in its spike protein. These changes could disrupt the ability of some – but probably not all – of the antibodies induced by current vaccines to bind to the spike protein. If this happens, the vaccines may be less effective in preventing people from becoming infected and passing on 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 coronavirus. In a new or updated vaccine, the mRNA instructions would encode the spike protein omicron.

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

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

A diagram showing how DNA becomes mRNA which becomes proteins.
By altering the mRNA sequence in a vaccine, researchers can alter the antibody-producing protein it codes for to better match the new variants. Alkov / iStock via Getty Images

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 the researchers have already published the genetic code for the spike omicron protein, all that remains is to create a DNA template for the spike protein that would be used to produce the mRNA portion of the new vaccines.

To do this, researchers mix DNA models with synthetic enzymes and four molecular building blocks that make up mRNA – G, A, U, and C for short. The enzymes then build a copy of mRNA from the DNA template, a process called transcription. Using this process, it only takes a few minutes to produce a batch of mRNA for the vaccines. The researchers then place the mRNA transcripts into fatty nanoparticles that protect the instructions until they are safely transmitted to the cells in your arm.

4. How long before a new vaccine is ready?

It only takes three days to generate the DNA template needed to make a new mRNA vaccine. Then it would take about a week to produce sufficient doses of mRNA vaccine for laboratory testing and an additional six weeks to perform preclinical testing on human cells in test tubes to ensure that a new vaccine works. like it should be.

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

While this trial is ongoing, manufacturers may start to change their current process to make a new vaccine. Ideally, once the clinical trial is complete – and if the vaccine is licensed or approved – a company could immediately begin rolling out doses of a new vaccine.

Dozens of vaccine vials on a table.
Moderna and Pfizer have both made statements saying they could have updated vaccine-ready vaccines in less than 100 days. AP Photo / Bruna Prado

5. Does an updated vaccine need full clinical trials?

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

At a minimum, 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 strains, beta and delta. If these are the only requirements, then researchers would only enlist hundreds – not tens of thousands – of people to obtain the necessary clinical data.

[The Conversation’s science, health and technology editors pick their favorite stories. Weekly on Wednesdays.]

One important thing to note is that if the vaccine makers decide to update their vaccines to the omicron variant, it wouldn’t be the first time that they have made this type of change.

A previous variant, B.1.351, appeared in October 2020 and was sufficiently resistant to the vaccines then in force to warrant updating. Manufacturers reacted quickly to the potential threat by developing an updated mRNA vaccine to match this variant and by performing clinical trials to test the new vaccine. Fortunately, this variant did not become the dominant variant. But if it did, vaccine makers would have been ready to roll out an updated vaccine.

If omicron – or any future variant, for that matter – turns out to warrant a new vaccine, companies have already completed dress rehearsals and are up to the challenge.

The conversation

Deborah Fuller, Professor of Microbiology, Faculty of Medicine, Washington University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

About Florence M. Sorensen

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