Antigenic landscape of a highly mutated SARS-CoV-2 spike in ongoing viral evolution
- 1School of Life Sciences, Global Health Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne 1015, Switzerland
Abstract
The ongoing emergence of SARS-CoV-2 variants in an increasingly immune-experienced population is largely enabled by the plasticity of the Spike protein, which lies at the frontline of host immune pressure. Here, we investigated how extensive remodeling of the N-terminal domain (NTD) in Spike influences its antigenic properties. Using BA.2.87.1, a variant heavily mutated in this domain, we found that even large deletions do not substantially disrupt overall Spike structure or pseudovirus infectivity. However, our structural and binding analyses revealed that the NTD exhibits increased flexibility and that interaction with a heme–metabolite, known to facilitate the exposure of an immunodominant epitope, is lost. These conformational effects, coupled with 33 NTD mutations, compromised the ability of human convalescent antibodies to engage this domain, contributing to their reduced neutralizing capacity. Consequently, BA.2.87.1-like variants may escape recognition by the preexisting NTD-targeting antibodies, potentially reducing protection. Together, our results highlight the intrinsic adaptability of the Spike beyond the receptor-binding domain, with implications for immune escape during viral evolution.
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BibTeX
@article{turelli2026antigenic,
title = {{Antigenic landscape of a highly mutated SARS-CoV-2 spike in ongoing viral evolution}},
author = {Priscilla Turelli and Elise Eray and Charlène Raclot and Didier Trono and Aleksandar Antanasijevic},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {2026},
month = oct,
doi = {10.1073/pnas.2608185123},
url = {https://doi.org/10.1073/pnas.2608185123},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Antigenic landscape of a highly mutated SARS-CoV-2 spike in ongoing viral evolution
AU - Priscilla Turelli
AU - Elise Eray
AU - Charlène Raclot
AU - Didier Trono
AU - Aleksandar Antanasijevic
PY - 2026
DA - 2026/10/28
JO - Proceedings of the National Academy of Sciences of the United States of America
DO - 10.1073/pnas.2608185123
UR - https://doi.org/10.1073/pnas.2608185123
AB - The ongoing emergence of SARS-CoV-2 variants in an increasingly immune-experienced population is largely enabled by the plasticity of the Spike protein, which lies at the frontline of host immune pressure. Here, we investigated how extensive remodeling of the N-terminal domain (NTD) in Spike influences its antigenic properties. Using BA.2.87.1, a variant heavily mutated in this domain, we found that even large deletions do not substantially disrupt overall Spike structure or pseudovirus infectivity. However, our structural and binding analyses revealed that the NTD exhibits increased flexibility and that interaction with a heme–metabolite, known to facilitate the exposure of an immunodominant epitope, is lost. These conformational effects, coupled with 33 NTD mutations, compromised the ability of human convalescent antibodies to engage this domain, contributing to their reduced neutralizing capacity. Consequently, BA.2.87.1-like variants may escape recognition by the preexisting NTD-targeting antibodies, potentially reducing protection. Together, our results highlight the intrinsic adaptability of the Spike beyond the receptor-binding domain, with implications for immune escape during viral evolution.
SN - 0027-8424
SN - 1091-6490
ER -