With each new SARS-CoV-2 variation that causes an increase in cases, a troubling concern arises: Could the virus someday develop a combination of changes that would allow it to completely elude human immune response?
According to a recent research published in Nature, the virus will have a hard time getting there. Researchers studied dozens of naturally occurring and laboratory-selected mutations, including those found in Delta and other concerning variants, and discovered that a future SARS-CoV-2 variant will need about 20 of the right mutations to become fully resistant to the antibodies produced in response to a coronavirus infection or vaccination.
Even if the virus achieves this genetic miracle, it will still be vulnerable to a better set of antibodies, such as those that arise after natural infection and are enhanced further by mRNA vaccines.
The findings imply that, if appropriately activated, our immune system is capable of dealing with the worst that the coronavirus has to offer in the near future. “Immunity is surprisingly broad in patients who fought COVID last year and later got mRNA vaccines,” says Paul Bieniasz, head of Rockefeller University’s Laboratory of Retrovirology. “This means that, while natural infection or vaccinations provide protection, they haven’t even come close to depleting the human immune system’s ability to develop a defense against this virus.”
Our antibodies, like the coronavirus, come in a variety of forms. That’s why even the Delta variety of SARS-CoV-2, which is the most infectious thus far, doesn’t completely evade human immune system. It may be able to evade some of our antibodies, but not all of them. However, Delta will not be the last form of SARS-CoV-2 we encounter. The virus continues to replicate at a rapid pace in big populations, with new mutations and variations appearing on a regular basis.
Fabian Schmidt and Yiska Weisblum, postdocs, set out to figure out which changes gave SARS-CoV-2 the upper hand over antibodies. They started by modifying a separate, innocuous virus to express SARS-CoV-2 spike protein on its surface as a safe stand-in for the coronavirus.
As the fake coronaviruses multiplied, some of them gained new mutations as they copied themselves incorrectly. After that, the researchers bathed the fake coronaviruses in plasma samples from patients who had recovered from COVID and chose the mutants that were immune to antibody neutralization.
After a few rounds of this, the researchers discovered a number of mutations in the same places as those found naturally in SARS-CoV-2 variations, including those identified in Delta or other variants of concern.
The researchers next developed a “polymutant” virus, which was a fake coronavirus with a spike protein that had 20 of the worst mutations all at once. This polymutant demonstrated near-complete resistance to antibodies produced by people who had been infected with SARS-CoV-2 or who had been immunized against it. “So the virus might mutate and avoid the bulk of our antibodies,” Bieniasz adds, “but the genetic barrier to that happening is pretty high.”
According to the findings of one group of people, human immune system will win the race against the evolving coronavirus in the long term. Antibodies produced by people who have been exposed to both spontaneous infection and vaccination are extraordinarily efficient. Previously, a Rockefeller team led by Michel Nussenzweig, Paul Bieniasz, and Theodora Hatziioannou, a Rockefeller research associate professor, discovered that after an infection has passed, antibodies continue to evolve over several months, improving their ability to bind tighter to the spike protein.
Receiving mRNA vaccinations increases those antibodies even more, boosting their numbers and enhancing their capacity to cope with numerous variations merely by attaching to the original sequence tighter and tighter.
Plasma from people who had been both infected and immunized neutralized the polymutant increase in the current investigation. It also neutralized the original SARS coronavirus and SARS-like viruses identified in bats and pangolins, as well as the six SARS-CoV-2 variations examined. Hatziioannou, who co-directed the study, adds, “Antibodies from this group of patients are very powerful and flexible.” “They are expected to provide protection against any future SARS-CoV-2 variations, as well as future coronavirus pandemics.”
More research is needed to see if booster injections can enhance antibodies in vaccinated persons who have never been infected with the coronavirus.