How Israeli Scientists Are Trying to Determine COVID Vaccine Efficiency Against Omicron

The COVID omicron genome includes about 50 mutations that did not exist in the original version of the virus, and 32 of them are in the spike protein that binds the virus to cells in the body

Ido Efrati
Ido Efrati
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Coronavirus cells.
Coronavirus cells.
Ido Efrati
Ido Efrati

What is the level of effectiveness of current coronavirus vaccines against the newly surfaced omicron variant? The question is worrying health officials in Israel – and around the world. In other words: Is the omicron variant capable of breaking through the immune system’s protection – immunity created either naturally after recovering from COVID-19 or artificially from being vaccinated.

The omicron genome includes about 50 mutations that did not exist in the original version of the virus, and 32 of them are in the spike protein that binds the virus to cells in the body and is responsible for evading the immune system. Today’s vaccines are based on the immune response to the spike protein.

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Of the 32 mutations on the spike protein, 15 are in the receptor-binding domain, the region to which most of the antibodies manufactured by the vaccine are directed. No more than three mutations were identified in the critical region of the binding domain on previous variants of the coronavirus, and the large number of the mutations in the omicron variant has led experts to expect that the effectiveness of the existing vaccines will be lower.

So how much lower? And what level of protection do the vaccines provide against symptomatic infection, serious illness and death from the omicron variant? What is their effectiveness in preventing infection from a variant that is more infectious? The answers to all these questions should begin to become known in the next few weeks – either through laboratory testing or analysis of real-world global epidemiological data as the new variant spreads.

The bottleneck

At this stage, however, the experts are watching and waiting for lab test results to determine how well the vaccines work against the omicron variant. The steps to be taken against it will be based on these results. In Israel, the testing is being carried out at the national virology lab at the Sheba Medical Center at Tel Hashomer.

“The bottleneck in tests of this kind is the amount of time it takes for the virus, which comes from clinical samples, to grow and reproduce in cell cultures. At the moment, we’re still waiting,” said Prof. Ella Mendelson, the director of the lab. Omicron, she explained, does not grow that quickly. “In this way, it's reminiscent of the British [alpha] variant, which also grew more slowly in cultures,” she remarked.

“From the moment we begin seeing a lot of dead cells, it means that it has started to grow. This stage of the test is not a process that can be speeded up, and in general, it lasts between five and 10 days. The other stages of the testing are more limited in time,” she said.

The entire testing process involves eight stages and will last between 15 days and three weeks. The first stage involves obtaining appropriate samples: It requires extracting a sample from a patient’s nasal and pharynx area at the height of the illness, when there is a high viral load in the throat.

The second stage involves the actual testing of the sample: When it arrives in the lab, a PCR test is conducted to measure the amount of the coronavirus that it contains. At the same time, cell cultures are prepared to be used to grow the cells. The cells used for the cultures are cloned from African green monkeys, and at that point in the process, special safety precautions are taken to prevent the virus from escaping from the laboratory and to protect the lab workers.

The lab in Tel Hashomer Hospital, on Wednesday.
Prof. Ella Mendelson outside Tel Hashomer Hospital, on Wednesday.

Next comes the initial growth of the virus in the cultures. A small amount is then placed in an incubator to permit it to grow further.

The fourth stage is monitoring and waiting: Every day the cells are examined with a special microscope. After a few days, the destruction of the cell tissue begins to be visible, confirming that the virus is replicating inside the cells. That process takes four to 10 days – depending on the virus.

The fifth stage is calibrating the supply of virus that has grown. Another round of seeding of the virus in the culture is carried out to determine the concentration of the virus in the samples. That creates an additional stock of cells that can be tested and analyzed later.

The sixth stage is an attempt to neutralize the virus in the culture. That's the stage at which the antibodies are confronted with the new variant. This is done by diluting the various samples of blood serum – from people who have recovered from COVID or were vaccinated. In the process, the virus’ response to the antibodies is tested.

The seventh stage is reading the results: Each sample of blood serum is studied at every level of dilution. Blood serum samples that contain a large quantity of antibodies, or antibodies that are highly effective against the virus, will manage to delay the destruction of the cells by the virus – until it reaches a very high level of dilution, in other words a very low concentration of antibodies. Blood serum samples that contain fewer antibodies, or less effective antibodies, will only manage to delay the cell destruction when slightly diluted.

“In practice, we examine the relative level of destruction of the cells. The more [the virus] manages to destroy more cells, it is a sign that the antibodies are of lower efficacy. The most resistant variant to the antibodies that we have seen so far in the lab is the beta variant,” Mendelson said, referring to the first variant discovered in South Africa.

The eighth stage is the calculation of the efficacy of the protection: The extent to which the patient's antibodies protect against the new variant is compared to that of other variants. A large range of comparisons is possible, including comparing the efficacy of antibodies from people who have recovered from COVID and those from people who have received various vaccine doses – or haven't been vaccinated at all.

The complexity of the immune system

“It’s a very controlled experiment, carried out in a very orderly process based on an identical protocol to make it possible to compare the different variants,” Mendelson explained. “We hope we’ll have enough of the virus to make the important comparisons soon,” she added.

But testing on cell cultures only simulates part of the human immune system – the antibodies. There are other aspects of the immune system such as killer cells (which are absent from the serum of test patients) and cytokines, which prompt the destruction of infected cells.

“The immune system cells and other mechanisms lead to the killing of infected cells. What we are testing is the first line of defense. That doesn’t mean there aren’t other lines. The other lines of defense, including the immune system cells, can prevent severe illness [and] keep the patient from deteriorating, but they are less effective in preventing infection. We see a correlation between these lines of defense, because in the end, the immune system’s defense depends on its ability to identify the virus and react quickly. Obviously people who have never been vaccinated and have no immune memory are the most vulnerable – because they don’t even have a first line of defense. Time passes until the body builds this line of defense. During this time, the virus isn’t sitting around and waiting. It’s spreading to the lungs and other places in the body, increasing the risk of severe illness,” Mendelson noted.

However, Mendelson added this: "The real test is the epidemiological picture among the population when a wave of cases of the illness arises.”

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