Cross-reactive T cell immunity against novel coronaviruses with pandemic potential, predictable from spike sequence conservation
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 Thwaites, Paul Klenerman, Susanna J Dunachie, Le Van Tan, , Nguyen To Anh, Nguyen Thi Thu Hong, Truong Hoang Chau Truc, Nguyen Thi Han Ny, Do Duong Kim Han, Le Kim Thanh, Lam Anh Nguyet, Cao Thu Thuy, Le Nguyen Truc Nhu, Tran Tan Thanh, 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, C Louise Thwaites, Guy Thwaites, Lin-Fa Wang, Beng Lee Lim, Raph L Hamers, Anuraj Shankar, Suwatrti Suwarti, Yanie Tayipto, Eva Simarmata, Ragil Dien, Juthathip Mongkolsapaya, Wanwisa Dejnirattisai, Warangkana Chantima, Narisara Chantratita, Prapassorn Poolchanuan, Vichapon Tiacharoen, Adul Dulsuk, Sophon Iamsirithaworn, Nick Day, Phaik Yeong Cheah, Tassawan Poomchaichote, Kanpong Boonthaworn, Gavin Screaton, Aiete Dijokaite-Guraliuc, Raksha Das, Chang Liu, Piyada Supasa, Muneeswaran Selvaraj, Susanna J Dunachie, Paul Klenerman, E Yvonne Jones, David I Stuart, Barbara Kronsteiner, Martha Zewdie, Priyanka Abraham, Jennifer Hill, Nghiem My Ngoc, Alba Grifoni, Alessandro Sette, Wee Chee Yap, Chee Wah Tan, Le Van TanAbstract
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.