How do scientists update coronavirus vaccines for omicrons?

If the omicron corona virus species is sufficiently different from the original species, the effectiveness of existing vaccines may be reduced. In that case, companies would probably need to upgrade their vaccines to better combat Omicron. Deborah Fuller, a microbiologist who has been studying mRNA and DNA vaccines for more than two decades, explains why we may need to upgrade existing vaccines and how the process works.

Corona virus and spike protein

In some vaccines, mRNA is used to make copies of spike proteins for immunity (spike is shown in red).

1. Why might vaccines need to be updated?

Basically, the question that arises is whether the virus has changed enough that the antibodies from the original vaccine are unable to detect and repel the new mutant species.

Coronaviruses use spike proteins to bind to ACE-2 receptors on the surface of human cells, infecting them in this way. All Covid 19 mRNA vaccines act as mRNA by providing instructions, directing cells to make a harmless copy of the spike protein. Spike protein then causes the human body to produce antibodies. If a person is then exposed to the corona virus, these antibodies bind to the corona virus spike protein, disrupting its ability to infect the person’s cells.

The omicron species contains a new pattern of mutations in its spike protein. These changes could impair the ability of some (but probably not all) of the current vaccine antibodies to bind to the spike protein. If this happens, vaccines will be less effective in preventing infection with the omicron species and its transmission to others.

۲. How will the new vaccine change?

Existing mRNA vaccines, such as vaccines made by Modern or Pfizer, encode one of the spike proteins of the primary strain of the coronavirus. In a new or updated vaccine, the mRNA instructions must encode the omechron spike protein.

By replacing the genetic code of the original spike protein with the new species code, the new vaccine produces antibodies that bind more efficiently to the omicron virus and prevent cell infection.

People who have already been vaccinated or have already been exposed to Covid 19 are likely to need only one booster dose of the new vaccine to protect not only against the new strain but also against the old strain that may still be circulating. If omicron can overcome delta, those who have not been vaccinated should only receive 2 to 3 doses of the updated vaccine. If both Delta and Omicron are in circulation, people will probably receive a combination of existing vaccines and upgraded vaccines.

Convert DNA to mRNA and protein

By changing the mRNA sequence in the vaccine, the researchers could modify the antibody-producing protein that the vaccine encodes to better suit the new species.

3. How is the vaccine updated?

To make an updated mRNA vaccine, you need two elements: the genetic sequence of a new concern species spike protein and a strand of DNA pattern used to make mRNA.

In most organisms, DNA provides instructions for making mRNA. Since the researchers published the genetic code for the omicron spike protein, all that needs to be done is to make a DNA template for the spike protein that can be used to make the mRNA part of the new vaccine.

To do this, the researchers mixed the DNA patterns with enzymes and four units of mRNA (G, A, U and C for short). The enzymes then make the mRNA version of the DNA pattern in a process called transcription. Using this process, the production of mRNA sets for use in the vaccine takes only a few minutes. The researchers then insert the mRNA transcripts into lipid nanoparticles that protect the instructions until they are delivered safely to your arm cells.

4. How long does it take to prepare a new vaccine?

It only takes three days to produce the DNA pattern needed to make a new mRNA vaccine. It then takes about a week for enough mRNA vaccine to be produced for testing in the laboratory, and then it takes six weeks for preclinical tests on human cells in the test tube to make sure the new vaccine is working as expected.

Thus, within 52 days, scientists can prepare an upgraded mRNA vaccine to enter the production process and begin production for use in human clinical trials. The trial will probably take several weeks, and in total, it will take about 100 days to update and test the new vaccine.

While the trial is underway, manufacturers can set to work and adjust their current process to make a new vaccine. Ideally, once the clinical trial is complete, and if the vaccine is approved, the company can start producing new vaccine doses immediately.

VACCINE production

Moderna and Pfizer say they can upgrade vaccines in less than 100 days and prepare for trials.

5. Does the updated vaccine require a complete clinical trial?

It is not clear at this time how much clinical information is needed to validate the updated Covid 19 vaccine. However, all components of the new vaccine will be the same as the previous vaccine. The only difference is in the few lines of genetic code that slightly alter the shape of the spike protein.

From a safety point of view, the upgraded vaccine is essentially the same as the vaccines that have been tested before. Because of these similarities, clinical trials may not be as up-to-date as those required for first-generation Covid vaccines.

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At a minimum, clinical trials for upgraded vaccines are likely to require safety testing and confirmation that the new vaccine produces an antibody level similar to that of the original vaccine against the primary, beta, and delta strains. If only these conditions were needed, researchers would employ only a few hundred people (not tens of thousands) to obtain the clinical information needed.

Of course, this is not the first time that vaccine manufacturers have decided to upgrade their vaccines for the Omicron species.

One of the previous species, B.1.351 (beta species), which appeared in October 2020, was sufficiently resistant to current vaccines that needed updating. Vaccine manufacturers responded quickly to this potential threat by making an updated mRNA vaccine to match this species, and conducted clinical trials to test the new vaccine. Fortunately, beta did not become dominant. But even so, the vaccine makers were ready to produce an updated vaccine.

If it turns out that Omicron or any future needs a new vaccine, companies have already trained and are ready to respond to this challenge.

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