Hunt on for future Covid mutations that cause treatments to lose potency
Scientists are to increase surveillance for new coronavirus mutations amid concerns that future strains of the virus could develop at least partial resistance to antibody treatments and Covid-19 vaccines.
There is no evidence that the mutations seen so far could help the virus evade vaccines or treatments now in development, but genetic analysis of circulating strains suggests that partially-resistant variants can emerge and spread among humans.
In a paper drawn up for the government’s Sage committee of experts, the UK Covid genomics consortium (CogUK) reports that a number of mutations have cropped up in the crucial “spike” protein which covers the virus like pins in a pin cushion and allows the pathogen to invade human cells.
Because many vaccines use the spike protein to generate immunity against the virus, mutations that subsequently change the spike can affect how well that immunity works.
“Anything that affects the spike protein can potentially change how either natural immunity or vaccineinduced immunity responds to the virus,” said Jeffrey Barrett, a geneticist and member of the consortium at the Sanger Institute near Cambridge.
The coronavirus that causes Covid-19 is genetically fairly stable, but it still acquires mutations, creating a multitude of lineages that geneticists can use to track the virus around the world and from outbreak to outbreak. By chance, some lineages will pick up mutations in the spike protein, a process called “antigenic change”. Many of these are likely to make the virus worse at spreading, but others may be neutral or even improve the virus’s ability to infect.
The potential risk comes if the virus accumulates mutations in the spike protein that change it enough for antibody treatments and vaccines to lose their potency. This could be most problematic for so-called monoclonal antibody treatments, of the type given to Donald Trump, where patients are infused with a mixture of two different types of antibodies. Vaccines tend to induce a greater variety of antibodies, so even if some are ineffective, the rest should still target the virus.
The scientists describe how in the spring more than 500 people in Scotland contracted coronavirus with a spike mutation known as N439K. The mutant version vanished during lockdown, but later re-emerged in Romania, Norway, Switzerland, Ireland, Belgium, Germany, and is now circulating in the UK. The mutation, and at least half a dozen others, show that the spike protein can change without destroying the virus’s ability to spread.
Scientists have shown already that coronavirus with the N439K mutation is resistant to at least one type of antibody that infected people can produce. The aim of the surveillance is to watch for future mutations that might, with time, make the virus resistant to a greater variety of antibodies.
The genetics consortium is setting up a group to monitor new and existing mutations to ensure that signs of potential resistance are spotted early. “It is particularly important that surveillance of antigenic change is established in the lead up to the roll out of a vaccination program in the UK, since many of the vaccines under development target the spike protein,” the paper states.
Paul Bieniasz, a virologist at Rockefeller University in New York, said it was important to monitor genetic variation in the virus’s spike protein in order to anticipate potential problems ahead, rather than because there is any immediate threat from currently circulating variants.
The sporadic emergence of antibody resistance mutations, such as N439K, is one reason most antibody therapies rely on a cocktail of two antibodies. But Bieniasz said that depending on how widely those treatments are used, “it will be important to monitor resistance to them in the same way that we monitor bacterial resistance to antibiotics, or HIV resistance to antiviral drugs.”
A single mutation would be unlikely to render a Covid-19 vaccine impotent, he added, but as the virus evolves over the coming years, pharmaceutical firms might need to reformulate vaccines to take account of genetic changes that arise in the virus.