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

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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Publication Details

Journal
Clinical & Experimental Immunology
Published
2026-10-29
DOI
https://doi.org/10.1093/cei/uxag068
Primary Topic
SARS-CoV-2 and COVID-19 Research
Type
article
Field-Weighted Citation Impact
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article

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

Priyanka Abraham, Le Mau Toan, Le Nguyen Truc Nhu, Warangkana Chantima et al.
Clinical & Experimental Immunology
SARS-CoV-2 and COVID-19 Research
article

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

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

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.

Clinical & Experimental Immunology
Centre for Human Genetics (GB), National University of Singapore (SG), Bangladesh Medical University (BD), Mahidol University (TH), University of Oxford (GB), NIHR Oxford Musculoskeletal Biomedical Research Centre (GB), Mahidol Oxford Tropical Medicine Research Unit (TH), Oxford University Hospitals NHS Trust (GB), Oxford University Clinical Research Unit (VN), Hospital for Tropical Diseases (VN)
Openalex Percentile: Top 12%
SARS-CoV-2 and COVID-19 Research
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