One mutation may have been crucial for the JN.1 variant of COVID-19 that spread rapidly around the world last year, showing how quickly viruses can adapt.
“The single mutation in JN.1 was key to evading antibody responses and that’s why it was able to spread around the world,” said Emanuele Andreano of the Tuscany Life Sciences Foundation in Italy.
JN.1, a variant of the Omicron variant, was first identified in Luxembourg in August 2023. As of the end of January, it accounted for 88%, 85% and 77% of recorded infections in the United States, the United Kingdom and Australia, respectively. Its predecessor, BA.2.86, had never accounted for more than 5% of known infections worldwide.
JN.1 and its descendants remain the most commonly reported COVID-19 variants worldwide, and Andreano and his colleagues wanted to investigate why it had spread so widely. Genetic sequencing had previously shown that the spike protein the virus uses to infect host cells has additional mutations compared to BA.2.86.
To learn more, Andreano and his colleagues analyzed 899 antibodies from blood samples taken previously from 14 people who had received two or three doses of an mRNA COVID-19 vaccine and had been confirmed to have been infected with an earlier variant.
The researchers added each of these antibodies to a dish of monkey cells along with the BA.2.86 SARS-CoV-2 virus. They found that 66 of 899 antibodies were able to stop BA.2.86 from infecting the cells. When they repeated the experiment with JN.1, only 23 antibodies were able to block infection.
The researchers then used computer simulations to test how a mutation in JN.1’s spike protein helped it evade neutralizing antibodies that block the virus from entering cells. They found that the mutation, which replaces a long amino acid called leucine with a shorter one called serine, weakened or completely blocked antibodies from interacting with the spike protein.
The antibodies that prevented JN.1 infection in monkey cells were collected from five of the 14 blood sample donors. These individuals had “super-hybrid” immunity that arose from three doses of the mRNA vaccine, one infection with the first SARS-CoV-2 variant identified in Wuhan, China, and then a second infection with the Omicron variant, according to Andreano. These antibodies may bind to other parts of the spike protein away from the mutation site and prevent JN.1 infection, Andreano said.
The study suggests that a single mutation may have been key to allowing JN.1 to evade neutralizing antibodies, but it still doesn’t cause any more severe disease than previous mutations, Andreano said.
That’s because there are many other parts of the immune system, such as T cells, that stop the virus from causing severe disease even if it doesn’t prevent infection, says Jonathan Ball of the Liverpool School of Tropical Medicine in the U.K. “Overall, people’s immunity remains strong,” Ball says.
The antibodies the researchers found are similar to those found previously in populations around the world, but the study is still small and needs to be replicated in larger groups, says Darran Bailey of the Pirbright Institute in the UK.
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