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Clin Exp Immunol . Cross-reactive T cell immunity against novel coronaviruses with pandemic potential, predictable from spike sequence conservation

tetano

Editor, Senior Moderator
Clin Exp Immunol

. 2026 Oct 30:uxag068.
doi: 10.1093/cei/uxag068. Online ahead of print.

Cross-reactive T cell immunity against novel coronaviruses with pandemic potential, predictable from spike sequence conservation​


Nguyen Thi Thu Hong 1 , Barbara Kronsteiner 2 , Tran Tan Thanh 1 , Martha Zewdie 2 , Mohammad Ali 3 4 , Nguyen To Anh 1 , Lam Anh Nguyet 1 , Nguyen Thanh Dung 5 , Le Mau Toan 5 , Juthathip Mongkolsapaya 6 7 8 , Chee Wah Tan 9 , Nguyen Thanh Truong 10 , Le Kim Thanh 1 , Le Nguyen Truc Nhu 1 , Cao Thu Thuy 1 , Nguyen Van Vinh Chau 11 , Guy Thwaites 1 2 , Paul Klenerman 3 12 13 , Susanna J Dunachie 2 8 13 , Le Van Tan 1 2 ; for SEACOVARIANTS Consortium

Collaborators, Affiliations Expand


Abstract​


Widespread SARS-CoV-2 infection and vaccination have reshaped global immunity to coronaviruses. Whether this immunity extends to animal sarbecoviruses with spillover potential remains unknown. We assessed cross-reactive memory T-cell responses to spike proteins from five relevant human angiotensin-converting enzyme 2 (hACE2)-dependent sarbecoviruses and MERS-CoV in healthcare workers in the UK and Vietnam. Limited SARS-CoV-2 specific or cross-reactive responses were seen in pre-pandemic samples. However, in samples collected from vaccinated donors at 3-24 months after booster vaccination, cross-reactive T-cell responses across the hACE2-dependent sarbecoviruses were detected. There was a strong correlation between the magnitude of responses and the level of viral sequence identity. This relationship was reproduced across cohorts in the UK and Vietnam. These findings indicate that post-pandemic populations possess measurable cellular immunity to genetically related sarbecoviruses and suggest that the degree of T-cell cross-recognition can be predicted from the spike protein sequence conservation. Such data provide an immunological framework for assessing vulnerability to future sarbecovirus spillover.

Keywords: T-cell response; coronaviruses; sarbecovirus; spike protein.
 
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