Cross-clade vaccination to overcome sarbecovirus or merbecovirus neutralization gaps

Wan Ni Chia; Feng Zhu; Samuel Mo Sheng Cheng; Wee Chee Yap; Abeer N Alshukairi; Yun Yan Mah; Mayfong Mayxay; Vilada Chansamouth; Andrew Letizia; Beng Lee Lim; et al.; John Crump; Lin-Fa Wang; Chee Wah Tan

doi:10.1016/j.celrep.2026.117444

Cross-clade vaccination to overcome sarbecovirus or merbecovirus neutralization gaps

Wan Ni Chia, Feng Zhu, Samuel Mo Sheng Cheng, Wee Chee Yap, Abeer N Alshukairi, Yun Yan Mah, Mayfong Mayxay, Vilada Chansamouth, Andrew Letizia, Beng Lee Lim, …

Cell reports, Vol.45(6), 117444

28/05/2026

: https://doi.org/10.1016/j.celrep.2026.117444

https://hdl.handle.net/10523/51254

surrogate virus neutralization test

henipavirus

spillover

vaccine

cross-neutralization

CP: immunology

cross-clade

neutralizing antibody

merbecovirus

sarbecovirus

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.

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Published (Version of record) Open Access

url

https://doi.org/10.1016/j.celrep.2026.117444

Published (Version of record)

: 9926871944301891
: Cross-clade vaccination to overcome sarbecovirus or merbecovirus neutralization gaps
: Wan Ni Chia
Feng Zhu
Samuel Mo Sheng Cheng
Wee Chee Yap
Abeer N Alshukairi
Yun Yan Mah
Mayfong Mayxay
Vilada Chansamouth
Andrew Letizia
Beng Lee Lim
et al.
John Crump
Lin-Fa Wang
Chee Wah Tan
: Centre for International Health
: Cell reports, Vol.45(6), 117444
: Elsevier
: 28/05/2026
: Refer to article for funding information
: Copyright © The Author(s) 2026. This work was first published in Cell Reports (Elsevier). This is an open access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial use, distribution and reproduction in any medium, provided the original work is properly attributed to the creator(s) and the source, is not altered, transformed, or built upon in any way, and a link to the Creative Commons license is provided.
: English
: Journal article