Could coronavirus mutations render mRNA vaccines irrelevant?

Top vaccine specialist explains how mutations work and why he believes the vaccines will continue to be vital in Israel’s fight against the pandemic

A health care worker prepares a coronavirus vaccine (photo credit: OLIVIER FITOUSSI/FLASH90)
A health care worker prepares a coronavirus vaccine
(photo credit: OLIVIER FITOUSSI/FLASH90)
The British mutation has entered the State of Israel and is making its rounds across the country.
According to the Health Ministry, at least 30 cases have been identified. And coronavirus commissioner Prof. Nachman Ash said Tuesday that those 30 cases infected at least 189 people – a ratio of 1:6. The reproduction rate of the normal or original coronavirus in Israel is currently around 1:1.27.
Now, Israel is locking down for the third time “to address the possible danger of the British mutation and the catastrophe that could occur here in a few weeks” if steps are not taken, according to Science and Technology Minister Izhar Shay.

What is the British mutation? How did it happen? And will the vaccine, with which more than 1.5 million Israelis have been inoculated, be effective against it?
The Jerusalem Post asked Prof. Jonathan Gershoni from the Shmunis School of Biomedicine and Cancer Research at Tel Aviv University to explain:

How does a virus mutate?
A virus hijacks a cell, which otherwise should be functioning as whatever that cell is, Gershoni explained.
“The hijacked cell then becomes totally devoted to replicating the virus and creating new viruses that then infect other cells, which then will be hijacked and get involved in replicating, and so on and so forth,” he said.
Each virus that is now being shed from the infected cells contains its own copy of the genetic material, known as the genome of that virus. The genome of the novel coronavirus is written in 30,000 letters of RNA (nucleotide bases).
A mutation occurs when a genome changes in some way during replication.
“Think about if you had to make handwritten copies of the genome – there is a very great likelihood of having a typographical error,” Gershoni explained. “So whereas in printing books or copying documents, typos are common and understandable, the same is true when replicating a genome. But we call those typos mutations, and the virus bearing those mutations is a mutant or variant.”

How often do mutations happen?
With replication, there is a direct relationship between how many copies are being made at a given time to the mutations that are going to be accumulated, he said. If the infection rate is low, then the number of mutations tends to be relatively small. Anytime the infection rate is enhanced, so will an increase in errors.

What is the impact of these ‘typographical’ errors?
“The single exchange of a letter could possibly have a profound effect,” Gershoni pointed out. For example: “My wife is tough” vs “my life is tough.” But he said that not all mutations necessarily have an impact on the virus.

What kinds of impact could mutations have?
There could be a mutation that increases the ability of a virus to become more infectious, and if so, then the virus would become more efficient in spreading within the community.
“This is our assessment of the United Kingdom mutation,” Gershoni noted. “It may be 50% to 70% faster at infecting cells, and that can have a profound effect on the dynamics of the epidemic.”

What are the other options?
The mutation could render the virus more pathogenic, he said, which would then cause a more severe disease.
“For the moment, fortunately, there is no indication that the current mutations render the virus as being more dangerous – that is directly causing a more serious disease,” Gershoni said. Though he noted that obviously the more people that become infected will lead to more people that may need to be hospitalized and could possibly die. “So we really need to take all measures to protect ourselves: wearing masks and social distancing.”
Studies have shown that age is the most significant determinant of how sick people get from COVID-19. The website Statista showed that in China during the first wave of the virus, the average person with a confirmed infection had a 2.3% chance of dying. But for people between 70 and 79 that percentage increased to 8%.
An analysis of people in England that was published over the summer by Nature, a leading scientific journal, found that people over the age of 80 were 20 times more likely to die from COVID-19 than those in their 50s.
A third effect of a mutation, according to Gershoni, is that the virus could become less susceptible to the neutralizing antibodies stimulated or induced through vaccination.
“For the moment, I don’t think this is a point of real concern,” he said.

Could a mutation ever be good for humans?
According to Gershoni, it could be that a given mutation “screws up the virus and interferes with its ability to infect the cells. Errors like those would make the virus less efficient and ultimately lead it to peter out. This happens all the time.”

If the virus has mutated, why do we believe that the vaccine will still work?
The way antibodies work to “knock out” the virus is to occupy the surface of a receptor-binding domain (RBD) that interacts with angiotensin-converting enzyme 2 (ACE2), the receptor used by SARS-CoV-2.
The RBD is located within the spike of the virus and is what allows it to dock and gain entry into cells it infects.
The question becomes, said Gershoni: To what extent are the antibodies produced against the original spike protein going to be able to recognize a modified spike protein, that is the mutant spike, and neutralize the variant viral strain?
The answer is that it depends how many mutations there are.
Gershoni equated the situation to what it is like for people today, wearing masks, to protect themselves from the coronavirus.
“People have numerous discriminating features that help us recognize one another,” he said. “Yet, nonetheless, people walking around with 50% of their faces covered by masks are still easily recognized.”
He added that “vaccines cause our bodies to develop multiple types of antibodies recognizing many overlapping aspects of the RBD, and therefore, a single mutation – or even two or three – in the RBD should not render the panel of neutralizing antibodies ineffective.”

Are the UK and South African mutations in the spike?
“We do know most definitely that some of the changes in the UK and South African mutations are in the spike,” he said.

Could these mutations also impact treatment of the virus?
Gershoni said that this is more likely.
US President Donald Trump received an experimental antibody treatment, for example, that bound to a region on the main surface of the spike protein.
“This therapy uses two unique antibodies as opposed to a broad collection of numerous antibodies,” such as are developed by vaccines, Gershoni explained. “If, in fact, the mutation affects the binding of precisely those antibodies used for therapy, then it may reduce the efficacy of that particular treatment.”

On Wednesday, Prof. Sharon Alroy-Preis, head of Public Health Services, told a Knesset committee that the South African variant is more disturbing than the UK mutation because it can cause severe morbidity among the young.
“Its effect on the vaccine is not yet clear, and there is a worrying preliminary study,” Alroy-Preis said, noting that “it is suspected that the effectiveness of vaccines against it is less good.

How could we learn if the vaccines will effectively neutralize these mutations and other variants that will emerge in the future?
According to Gershoni, the most direct way of testing this would be if Pfizer or Moderna, for example, used serum taken from the vaccinated participants in the Phase III clinical trial and tested their ability to inactivate and neutralize the mutant viruses and other strains in laboratory experiments.
“I expect that this is what is being done,” he said. “The concerns raised by scientists and practitioners in the absence of such controlled experiments are for the moment theoretical.”

So, is there a danger that the Pfizer and Moderna vaccines are no longer effective?
“I honestly don’t believe so,” said Gershoni. “Therefore we must continue to aggressively vaccinate.”