@article{becccf1cea7e44d494f2183ffb9a9510,
title = "Cross-clade vaccination to overcome sarbecovirus or merbecovirus neutralization gaps",
abstract = "The coronavirus disease 2019 (COVID-19) pandemic highlights the importance of identifying high risk pathogens, defining the immunity gaps and developing preemptive vaccination strategies. Here, we establish a high-resolution surrogate virus neutralization test detecting neutralizing antibodies against multiple virus families simultaneously, demonstrating good concordance with traditional assays. Extensive serosurveillance of pre-pandemic sera from different continents reveals low prevalence human exposures to different beta-coronaviruses, and identifies individuals with prior exposure to ACE2-binding MERS-like viruses. Furthermore, COVID-19 vaccination induces significant cross-neutralizing antibodies against clade 1b, 1c, and 3 but not clade 1a sarbecoviruses. Similarly, MERS and Nipah convalescent sera neutralize cognate viruses but have limited cross-neutralization against other related merbecoviruses and henipaviruses that utilize DPP4 and ephrin B2 receptors. Finally, a cross-clade prime-and-boost vaccination strategy using antigenically distinct antigens could induce broadly neutralizing antibodies against related viruses beyond vaccine antigens, supporting broad-spectrum beta coronavirus vaccine development.",
keywords = "cross-clade, cross-neutralization, henipavirus, merbecovirus, neutralizing antibody, sarbecovirus, spillover, surrogate virus neutralization test, vaccine",
author = "Chia, \{Wan Ni\} and Feng Zhu and Cheng, \{Samuel Mo Sheng\} and Yap, \{Wee Chee\} and Alshukairi, \{Abeer N.\} and Mah, \{Yun Yan\} and Mayfong Mayxay and Vilada Chansamouth and Andrew Letizia and Lim, \{Beng Lee\} and Yidan Wang and Kwek, \{Madeline Sheng Si\} and Evans, \{Tierra Smiley\} and Ohnmar Aung and Thu, \{Hlaing Myat\} and Johnson, \{Christine K.\} and Yanqun Wang and Jincun Zhao and Manning, \{Jessica E.\} and Christina Yek and Chanthap Lon and Seng Heng and Sovann Ly and Rithea Leang and Rekol Huy and Dewantari, \{Aghnianditya Kresno\} and Yudhaputri, \{Frilasita Aisyah\} and Myint, \{Khin Saw Aye\} and Rubach, \{Matthew P.\} and Crump, \{John A.\} and Maro, \{Venance P.\} and Moreland, \{Nicole J.\} and Aimee Paterson and Richard Charlewood and Jingjing Song and Shiwei Chen and Tan, \{Wan Yi\} and Mok, \{Chris Ka Pun\} and Hor, \{Catherine Hong Huan\} and David Lye and Hui, \{David SC\} and Young, \{Barnaby E.\} and Malik Peiris and Wang, \{Lin Fa\} and Tan, \{Chee Wah\}",
note = "This work was supported in part by grants from the Singapore National Medical Research Council (OFLCG19May-0034 and MOH-000696) awarded to L.F.W., the Singapore Programme for Research in Epidemic Preparedness and Response (PREPARE) (PREPARE-CS1-2023-011, PREPARE-UKRI-SF-2025-004, and PREPARE-SF-2024-012), the National University Hospital (NUHS/2023/018/Startup/10), and the Wellcome Trust (grant no. 226120) awarded to C.W.T. Sample collection in Laos was supported by the National Institute of Allergy and Infectious Diseases, National Institutes of Health, under contract no. U01AI15180 and the Armed Forces Health Surveillance Branch (AFHSB) Global Emerging Infections Surveillance program (GEIS) work unit number PROMIS ID P00034\_17\_N2. We would like to thank Prof. Paul Newton, Prof. Matthew Robinson, and Dr. Danoy Chommanam and the patients in LOMWRU and Laos who coordinated and participated in the study, respectively. Sample collection in Cambodia was supported in part by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases. Sample collection in Myanmar was supported by the National Institute of Health and the National Institute of Allergy and Infectious Diseases, under contract nos. U01Al151814, K01TW010279, and R21AI175905. The project and sample collection in Indonesia was supported by the US CDC for the project detecting emerging vector-borne zoonotic pathogens in Indonesia (5R18CK000278-03, 5R18CK000278-03, 5U18CK000443-04, and 6U18CK00043-05-01). Sample collection in Tanzania was funded by the US National Institutes of Health National Institute of Allergy and Infectious Diseases (grant no. R01AI121378) that also provided support to J.A.C., V.P.M., and M.P.R. This project was partly supported by the Collaborative Research Fund \#C2103-20G from the Hong Kong Research Grant Council to C.H.H.H. and C.W.T. Nipah convalescent samples were provided as part of the WHO collaborative study for the development of International Standard for anti-Nipah antibody coordinated by the MHRA (NIBSC) in partnership with CEPI. We thank Mr. Leo CH Tsang from Hong Kong University for providing assistance in study. A.L. (CAPT, USN, MC) is a military service member. This work was prepared as part of his official duties. Title 17, USC, §105 provides that copyright protection under this title is not available for any work of the US government. Title 17, USC, §101 defines a US government work as a work prepared by a military service member or employee of the US government as part of that person{\textquoteright}s official duties. The views expressed in the article are those of the authors and do not necessarily express the official policy and position of the US Navy, the Department of Defense, or the US government. Publisher Copyright: {\textcopyright} 2026 The Author(s). Published by Elsevier Inc. ",
year = "2026",
month = jun,
day = "23",
doi = "10.1016/j.celrep.2026.117444",
language = "English",
volume = "45",
journal = "Cell Reports",
issn = "2639-1856",
publisher = "Cell Press",
number = "6",
}
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