Although much is still unknown, what we know about this new variant tells us important things about the virus: it can adapt to become more easily transmissible and may be able to become more difficult to neutralize and possibly be able to overcome the vaccine to a small extent.
So far, SARS-CoV-2 has mutated at a very stable rate, with only one or two variations per month. Some variations have caused scientists to stop, sometimes mutating to become more transmissible and other times to become more effective in avoiding detection by our immune system. But with this new variant, called B.1.1.7, the virus acquired 17 mutations at once that alter the virus’s proteins, according to the Centers for Disease Control and Prevention, which affect four different viral proteins: the protein spike, ORF1ab, Orf8 and protein N, the main nucleocapsid.
While the sheer number of mutations in a variant is worrying, what is perhaps more worrying is how the mutations, taken together, can change the way the virus works. One of the mutations, N501Y, increases the strength with which the spike protein binds to the human ACE2 receptor, which can make it easier for the virus to take root in infected people. This mutation is probably the reason why this new variant, first isolated in the UK in late September, now accounts for more than 60% of new infections in and around London.
A second mutation in the spike protein, 69-70del, excludes two amino acids, the removal of which can allow the virus to prevent some immune responses and, combined with another mutation, can make it more transmissible. The 69-70del mutation has been found in other variant strains – including the mink strain in Denmark – and appears to occur when patients carry the virus for several months under immune pressure, not necessarily from the patient’s own immune system, but from treatments such as plasma convalescent that pumps antibodies into the patient’s system.
A third mutation, P681H, occurs in what is called the spike protein cleavage site, which is an area known to affect how quickly the virus can enter and kill cells. Changes in this part of the virus can potentially increase its ability to cause disease – and its lethality – although there is still no evidence to show that this new variant is more dangerous for humans. This mutation alone is already unsettling. The fact that it is combined in this variant strain with another mutation in the Orf8 protein, which can also increase pathogenicity, is cause for alarm.
The mutations that affect the two other proteins – ORF1ab and the N protein – are also suspected of allowing the virus to replicate more quickly and avoid the immune system, although much more research is needed to see how each of these 17 mutations affects how the virus works. Still, we know enough to make some assumptions.
First, SARS-CoV-2 knows how to adapt and adapt quickly, like the flu virus. We must therefore be prepared for the possibility that the virus will remain with us for a long time. Like a flu vaccine, a Covid-19 vaccine may not be a definitive vaccine. We already know from a recent study published in the New England Journal of Medicine that the half-life of neutralizing antibodies in at least one of the vaccines, the Modern vaccine, decreases relatively quickly over a period of three months in those that respond more vigorously and shorter. in those who mount a less vigorous response. Although the study was small, it questions whether a vaccine taken today would remain effective 12 months, 18 months or more in the future. B.1.1.7 tells us something new – not only can immunity weaken, but the potency of the vaccine itself can change if the virus changes. This is not to say that modern medicine cannot keep up with the evolution of the Covid-19 virus, as with the flu. But it may not be as simple or easy as many expected.
Second, with the 69-70del mutation, we may be facing a medical paradox. In an effort to save the lives of immunocompromised people who were infected with the virus, providers sometimes administered several rounds of antibody treatments to their patients. In some cases, patients recover after a round of treatment only to become ill again and need another dose. Even in a single patient, immune suppression over a period of weeks and sometimes months gives the virus a multitude of opportunities to learn our best defenses and mutate to become more effective in escaping our immune system. While administering antibody treatments could save a human life, a UK study has hypothesized that it could also facilitate the creation of new strains of the virus.
Finally, the variant suggests that we should immediately start planning the next generation of Covid vaccines to respond more effectively to a mutating virus. There should be hope that authorized vaccines are already being tested against the new variant. The companies expressed confidence that their vaccine could protect against it, with BioNTech noting that their vaccine could be changed to combat the new variant.
Still, it is worth studying further the targets of alternative vaccines that may prove more effective in protecting the population against variants of the virus. At the moment, most vaccines under development target the protein spike. This includes the Moderna, Novovax and Johnson & Johnson vaccines, as well as vaccines based on adenovirus, such as those from AstraZeneca. These vaccines may work against the current version of the virus, but if we want to stay ahead of the spread of the disease, we need to expand vaccine targets to include other proteins like the ORF1ab, Orf8 and N proteins or the ORF3b protein, which others have studied. Other countries have developed vaccines using more traditional methods, using inactivated whole viruses. This type of vaccine, or other vaccines that target multiple proteins at the same time, may be the best approach in the future.
I often compare viruses to code-breaking machines, continually running numbers until I find a new way to explore any ecological niche they inhabit – trillions of copies of a single virus, each changing and adapting to each new challenge. Sometimes, we come across a virus that learns to break our defenses faster than we can rebuild them. I fear that SARS-CoV-2 may be one of them.