COVID-19 vaccines may need to be upgraded after scientists identified a mutation in the spike protein of SARS-CoV-2, allowing the virus to evade important immune cells.
The P272L Spike mutation first arose during the second UK COVID-19 wave, in September 2020, and is found on the part of the Spike protein most frequently recognised by killer T-cells.
The “escape mutation” has been found so far in more than 100 viral lineages, including those classed as variants of concern, and has been seen in strains in the UK and Europe, as well as in Australia and the USA between September 2020 and March 2022.
A new study led by Cardiff University, UK, also including scientists at the University of Oxford and the COVID-19 Genomics UK consortium, has shown how the P272L Spike mutation escaped recognition by killer T-cells in a group of healthcare workers from south Wales early in the pandemic.
Writing in *Cell*, they add the mutation also evaded all T-cells raised against this part of the virus in donors that had been vaccinated.
Lead author Professor Andrew Sewell, from Cardiff University’s School of Medicine and Systems Immunity Research Institute, said: “We studied more than 175 different types of killer T-cells that could see the part of the virus containing the P272L mutation and were surprised to see that this one mutation resulted in escape in all the donors studied.
“Similar escape mutations have been seen in influenza viruses. It has been estimated the virus that caused the 1968 Hong Kong flu pandemic has mutated to escape from recognition by a type of killer T-cell once every three years.”
In this study, P272L escaped from more than 175 T-cell receptors – both in COVID patients and in individuals who had been vaccinated.
Since the Cardiff study was completed, the mutation has also been observed in the original Omicron variant (BA.1) in England.
Professor Tom Connor, an expert in SARS-CoV-2 genomics from Cardiff University’s School of Biosciences and Systems Immunity Research Institute, said: “The P272L mutation has arisen in many different SARS-CoV-2 lineages since the start of the pandemic. The independent evolution of the same mutation in multiple viral lineages is an example of homoplasy, which may be suggestive of a mutation that could confer a selective advantage.
“I anticipate that we may see more occurrences of the P272L variant over time, as the virus continues its evolution into a human pathogen. Our work emphasises how much we still have to learn about SARS-CoV-2, and the importance of monitoring T-cell escape in future.”
Dr Lucy Jones, clinical research lead from Cwm Taf Morgannwg University Health Board, added that while current vaccines work well and should still be taken up, its research suggests vaccines may need altering as more is known about the virus.
Dolton G, Rius C, Hasan MS et al. Emergence of immune escape at dominant SARS-CoV-2 killer T-cell epitope. *Cell* 14 July 2022
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