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

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ID: 338052
2026
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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.
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Authors Nguyen Thi Thu Hong, Barbara Kronsteiner, Tran Tan Thanh, Martha Zewdie, Mohammad Ali, Nguyen To Anh, Lam Anh Nguyet, Nguyen Thanh Dung, Le Mau Toan, Juthathip Mongkolsapaya, Chee Wah Tan, Nguyen Thanh Truong, Le Kim Thanh, Le Nguyen Truc Nhu, Cao Thu Thuy, Nguyen Van Vinh Chau, Guy Edward Thwaites, Paul Klenerman, Susanna Jane Dunachie, Le Van Tan, Thi Thu Thao Le, Truong Hoang Chau Truc, Nguyen Thi Han Ny, Do Duong Kim Han, Lam Minh Yen, Vu Thi Ty Hang, Pham Tieu Kieu, Vo Tan Hoang, Nguyen Thi Thao, Mary Chambers, Vu Duy Thanh, H. Rogier van Doorn, Trinh Son Tung, Louise Thwaites, Lin-Fa Wang, Beng Lee Lim, Raph L Hamers, Anuraj Shankar, Suwatrti Suwarti, Yanie Tayipto, Eva Simarmata, Ragil Dien, Wanwisa Dejnirattisai, Warangkana Chantima, Narisara Chantratita, Prapassorn Poolchanuan, Vichapon Tiacharoen, Adul Dulsuk, Sopon Iamsirithaworn, Nick Day, Phaik Yeong Cheah, Tassawan Poomchaichote, Kanpong Boonthaworn, Gavin Robert Screaton, Aiete Dijokaite-Guraliuc, Raksha Das, Chang Liu, Piyada Supasa, Muneeswaran Selvaraj, E Yvonne Jones, D. I. Stuart, Priyanka Abraham, Jennifer W Hill, Nghiêm My Ngoc, Alba Grifoni, Alessandro Sette, Wee Chee Yap
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Journal Clinical & Experimental Immunology
Year 2026
DOI
10.1093/cei/uxag068
URL
https://academic.oup.com/cei/advance-article-pdf/doi/10.1093/cei/uxag068/72612127/uxag068.pdf
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