ANs scientists try to track the spread of a new, more infectious coronavirus variant around the world – finding more cases in the United States and elsewhere this week – they are also eyeing a different mutation with potentially greater implications for Covid’s effectiveness – 19 vaccines work.
The mutation, identified in one variant seen for the first time in South Africa and seen separately in another variant in Brazil, changes a part of the virus that the antibodies in your immune system are trained to recognize after you are infected or vaccinated. Laboratory studies show that the change could make people’s antibodies less effective in neutralizing the virus. The mutation appears to help the virus to disguise part of its characteristic appearance, so the pathogen may find it easier to escape immune protection.
It is not that the mutation renders existing vaccines useless, the scientists emphasize. Vaccines authorized so far and those under development produce what is called a polyclonal response, generating numerous antibodies that lodge in different parts of the virus. Changes in any of these target sites increase the possibility that vaccines are less effective, not that they will not work.
advertising
“With one mutation or even three mutations, antibodies are expected to still recognize this variant, although they may not recognize it as well as other variants,” said Ramón Lorenzo-Redondo, molecular virologist at the Feinberg School of Medicine at Northwestern University.
Basically, the mutation is getting attention because it seems more likely to have an effect on vaccines than other mutations that have emerged, although scientists are still trying to test that hypothesis. The most contagious variant that generates global alarms, which was first seen in the UK and is referred to as B.1.1.7, is not considered to have mutations that will greatly affect vaccines, according to the evidence so far.
advertising
“We need to monitor these mutations,” said Jesse Bloom, an evolutionary virologist at Fred Hutchinson Cancer Research Center, who published an article on this specific mutation, known as E484K, with colleagues.
But Bloom added that he believed the virus would have to catch multiple mutations – and particular mutations at specific points, not just any changes – to have a serious effect on the vaccine’s effectiveness, which is likely to take some time.
“I am quite optimistic that, even with these mutations, immunity will not suddenly fall on us,” said Bloom. “It may be corroded gradually, but it will not fail for us, at least in the short term.”
Scientists think the coronavirus may eventually change so much that the immunity provided by the vaccines will be threatened, a process that will increase as the number of people protected from the virus – whether through vaccination or infection – increases and the evolutionary pressure in turn increases. But they still predict that it could take years and that, when it does, vaccine manufacturers can adjust their designs to match the latest variant, a process that some companies said would take only weeks.
The SARS-CoV-2 coronavirus, which causes Covid-19, mutates as it spreads, as do other viruses. Many of the mutations do nothing and some may even prevent the virus from seeking to replicate and spread. But every now and then, a random mutation gives the virus an evolutionary advantage and that variant can then become dominant. At the beginning of the pandemic, a mutation known as D614G helped the coronavirus to spread more easily, and variants with this mutation quickly outnumbered others globally.
B.1.1.7, which has since spread to other parts of the world, appears to be even more infectious, with some estimates saying it is 50% more transmissible. One of its mutations, called N501Y, improves how well the virus’s spike protein can bind to a receptor called ACE2 in human cells, making it more likely that the virus will successfully infect cells and pass from person to person.
The same N501Y mutation is also present in the variant identified in South Africa, although the two variants have evolved independently. (Public health officials are trying to prevent people from using terms like “UK variant” or “South Africa variant”, just as they discourage people from linking SARS-2 by name to China or Wuhan. “We need to use the names properly because we don’t want to stigmatize where these variants were identified,” said Maria Van Kerkhove of the World Health Organization on Tuesday. “This is true for any virus that is identified.”)
The inclusion of N501Y appears to help the South African variant to spread faster as well, but the variant also has the E484K mutation, unlike the variant that first appeared in the UK. mutations in the same part of the virus have appeared previously during the pandemic, the specific E484K mutation is attracting more interest now, partly because it is in this variant that is spreading across South Africa and, through travelers, has started to appear elsewhere, including Japan, Norway and the United Kingdom
The E484K change occurs in a part of the spike protein called the receptor-binding domain, which plays a crucial role when the virus binds to ACE2 and is a key target for antibodies. As laboratory studies have shown, antibodies do not recognize variants with E484K, as well as other forms.
Research by Bloom and colleagues this week added further to that evidence. In their study, which involved mapping how antibodies from people who recovered from Covid-19 fared against different variants, the scientists found that mutations like E484K had the greatest impact on the antibodies’ ability to block the virus, with some people experiencing more than 10 times drop in neutralization against the variant. The researchers called the location of the E484K mutation “the site of greatest concern for viral mutations”. (There was variability between samples, however; some people were able to neutralize the variant perfectly, and mutations elsewhere had a greater impact than the E484K for certain people.)
Bloom’s study focused on people who had recovered from an infection, not those who had been vaccinated; researchers around the world are investigating how well current vaccines resist different variants.
But despite what he and his colleagues found about E484K, Bloom noted that the mutation only reduced neutralizing activity, and did not eliminate it. Current vaccines, in turn, have shown that they can generate strong immune responses. “I am confident that current vaccines will be useful for quite some time,” wrote Bloom in a Twitter topic detailing the research.
The most urgent concern for the time being, scientists say, remains the spread of B.1.1.7, the variant seen for the first time in the UK. Although it is not believed to cause more serious cases of Covid-19, if it causes more cases in general because it spreads more easily, it will lead to more hospitalizations and deaths. It is also probably more difficult to control than other variants and raises the limit on the percentage of the population that needs to be protected to achieve collective immunity.
“The variant is really very important,” said Marc Lipsitch, an epidemiologist at Harvard’s School of Public Health TH Chan.
Lipsitch said the United States should focus its efforts on restricting the variant, including sequencing more patient samples to identify cases and targeting its contact and quarantine tracking campaigns to try to restrict it.
“As far as we can locate them and preferentially stop the spread, it will not be perfect, it will be far from perfect, but anything we can do to delay the spread of this new variant virus will make control easier and help us in the race to vaccinate more people before it becomes more common, ”he said.