The covid-19 variant JN.1 may have been able to evade antibodies and spread globally due to one critical mutation to its spike protein.
One mutation may have been crucial to the covid-19 variant JN.1 spreading rapidly around the world last year, demonstrating how quickly the virus can adapt.
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| JN.1 spread widely despite many people being vaccinated and having previous covid-19 infections Debarchan Chatterjee/NurPhoto/Shutterstock |
“A single mutation in JN.1 was key for it to evade the antibody response, and that’s why it was able to spread globally,” says Emanuele Andreano at the Toscana Life Sciences Foundation in Italy.
JN.1, a subvariant of the omicron variant, was first identified in Luxembourg in August 2023. At the end of January, it accounted for 88 per cent, 85 per cent and 77 per cent of the recorded infections in the US, UK and Australia, respectively. Its predecessor, BA.2.86, never accounted for more than 5 per cent of known global infections.
With JN.1 and its descendants remaining the most reported covid-19 variants globally, Andreano and his colleagues wanted to investigate how it spread so widely. Genetic sequencing previously pointed to an additional mutation compared with BA.2.86 in its spike protein, which the virus uses to infect host cells.
To learn more, Andreano and his colleagues analysed 899 types of antibodies from blood samples previously collected from 14 people, all of whom had received two or three doses of an mRNA covid-19 vaccine and had confirmed infections with prior variants.
The researchers added each of these antibodies, along with BA.2.86 SARS-CoV-2 viruses, to a dish containing monkey cells. This revealed 66 of the 899 antibodies were able to prevent BA.2.86 from infecting the cells. When they repeated the experiment with JN.1, just 23 of the antibodies prevented infection.
Next, the researchers used a computer simulation to test how JN.1’s spike protein mutation might have helped it evade neutralising antibodies, which stop viruses from entering cells. They found the mutation caused a longer amino acid called leucine to be swapped for a shorter one called serine, which then either weakened or entirely blocked the antibodies from interacting with the spike protein.
The antibodies that prevented JN.1 infections in the monkey cells came from five of the 14 blood sample donors. These individuals had “super hybrid” immunity, says Andreano, brought about from receiving three mRNA vaccine doses, being infected once by the original SARS-CoV-2 variant identified in Wuhan, China and infected again by an omicron variant. Those antibodies may bind to other parts of the spike protein, away from the site of the mutation, thereby preventing a JN.1 infection, says Andreano.
The study shows how a single mutation may have been key to JN.1 evading neutralising antibodies. However, it still doesn’t cause more severe illness than prior variants, says Andreano.
That is probably because there are many other prongs of the immune system, such as T-cells, that work to stop the virus from causing severe illness even if they can’t prevent infection, says Jonathan Ball at the Liverpool School of Tropical Medicine in the UK. “Collectively, people’s immunity is holding strong,” he says.
The antibodies the researchers collected are similar to those previously found in populations worldwide. But the study is still small and should be replicated in larger groups, says Dalan Bailey at The Pirbright Institute in the UK.
Journal reference:
Science Immunology DOI: 10.1126/sciimmunol.adp9279
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