Antibody evasiveness of SARS-CoV-2 subvariants KP.3.1.1 and XEC
Qian Wang, Yicheng Guo, Ian A Mellis, Madeline Wu, Hiroshi Mohri, Carmen Gherasim, Riccardo Valdez, Lawrence J Purpura, Michael T Yin, Aubree Gordon, David D Ho
Cell Reports, doi:10.1016/j.celrep.2025.115543
Highlights d KP.3.1
AUTHOR CONTRIBUTIONS The study was conceptualized by Q.W., Y.G., I.A.M., and D.D.H. Experiments were conducted and data analyzed by Q.W., Y.G., I.A.M., and M.W. Project management was handled by Q.W. Serum samples were collected by H.M., C.G., R.V., L.J.P., M.T.Y., A.G., and their colleagues. The results were analyzed and the manuscript was written by Q.W., Y.G., M.W., I.A.M., and D.D.H. All contributing authors have reviewed and endorsed the manuscript.
DECLARATION OF INTERESTS D.D.H. co-founded TaiMed Biologics and RenBio, and he serves as a consultant for WuXi Biologics and Brii Biosciences and is a board director at Vicarious Surgical. A.G. served as a member of the scientific advisory board for Janssen Pharmaceuticals and has consulted and serves on a scientific advisory board for Sanofi Pasteur.
STAR+METHODS Detailed methods are provided in the online version of this paper and include the following:
STAR+METHODS KEY RESOURCES TABLE EXPERIMENTAL MODEL AND SUBJECT DETAILS
Clinical cohorts Serum samples were collected as part of the VIVA study at the University of Michigan 14, 18 and as part of the ''COVID-19 Persistence and Immunology Cohort (C-PIC)'' study at Columbia University. Specimens were obtained following participant informed consent and in adherence to the protocols approved by the Institutional Review Board of the University of Michigan Medical School (protocol HUM00232359) and Columbia University (protocol AAAS9722), respectively. In this study,..
References
Arora, Happle, Kempf, Nehlmeier, Stankov et al., Impact of JN.1 booster vaccination on neutralisation of SARS-CoV-2 variants KP.3.1.1 and XEC, Lancet Infect. Dis,
doi:10.1016/S1473-3099(24)00688-1Earle, Ambrosino, Fiore-Gartland, Goldblatt, Gilbert et al., Evidence for antibody as a protective correlate for COVID-19 vaccines, Vaccine,
doi:10.1016/j.vaccine.2021.05.063Feng, Yuan, Powers, Hu, Munt et al., Broadly neutralizing antibodies against sarbecoviruses generated by immunization of macaques with an AS03-adjuvanted COVID-19 vaccine, Sci. Transl. Med,
doi:10.1126/scitranslmed.adg7404Li, Faraone, Hsu, Chamblee, Liu et al., Immune Evasion, Cell-Cell Fusion, and Spike Stability of the SARS-CoV-2 XEC Variant: Role of Glycosylation Mutations at the N-terminal Domain,
doi:10.1101/2024.11.12.623078Liu, Wang, Nair, Yu, Rapp et al., Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike, Nature,
doi:10.1038/s41586-020-2571-7Liu, Yu, Jian, Yang, Song et al., Enhanced immune evasion of SARS-CoV-2 KP.3.1.1 and XEC through NTD glycosylation,
doi:10.1101/2024.10.23.619754Liu, Yu, Jian, Yang, Song et al., Enhanced immune evasion of SARS-CoV-2 variants KP.3.1.1 and XEC through N-terminal domain mutations, Lancet Infect. Dis,
doi:10.1016/S1473-3099(24)00738-2Simon, Kota, Bloomquist, Hanley, Forgacs et al., PARIS and SPARTA: Finding the Achilles' Heel of SARS-CoV-2, mSphere,
doi:10.1128/msphere.00179-22Smith, Lapedes, De Jong, Bestebroer, Rimmelzwaan et al., Mapping the antigenic and genetic evolution of influenza virus, Science,
doi:10.1126/science.1097211Uriu, Kaku, Uwamino, Fujiwara, Saito et al., Robust antiviral humoral immunity induced by JN.1 monovalent mRNA vaccines against a broad range of SARS-CoV-2 Omicron subvariants including JN.1, KP.3.1.1 and XEC,
doi:10.1101/2024.11.20.624471Wang, Guo, Bowen, Mellis, Valdez et al., XBB.1.5 monovalent mRNA vaccine booster elicits robust neutralizing antibodies against XBB subvariants and JN.1, Cell Host Microbe,
doi:10.1016/j.chom.2024.01.014Wang, Guo, Ho, Ho, Activity of Research-Grade Pemivibart against Recent SARS-CoV-2 JN.1 Sublineages, N. Engl. J. Med,
doi:10.1056/NEJMc2410203Wang, Iketani, Li, Liu, Guo et al., Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants, Cellule,
doi:10.1016/j.cell.2022.12.018Wang, Mellis, Ho, Bowen, Kowalski-Dobson et al., Recurrent SARS-CoV-2 spike mutations confer growth advantages to select JN.1 sublineages, Emerg. Microb. Infect,
doi:10.1080/22221751.2024.2402880Wang, Mellis, Wu, Bowen, Gherasim et al., KP.2-based monovalent mRNA vaccines robustly boost antibody responses to SARS-CoV-2, Lancet Infect. Dis,
doi:10.1016/S1473-3099(25)00058-1Wang, Muecksch, Cho, Gaebler, Hoffmann et al., Analysis of memory B cells identifies conserved neutralizing epitopes on the N-terminal domain of variant SARS-Cov-2 spike proteins, Immunity,
doi:10.1016/j.immuni.2022.04.003Zhang, Lindenberger, Parsons, Thakur, Parks et al., SARS-CoV-2 Omicron XBB lineage spike structures, conformations, antigenicity, and receptor recognition, Mol. Cell,
doi:10.1016/j.molcel.2024.06.028DOI record:
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"DOI": "10.2807/1560-7917.ES.2017.22.13.30494",
"article-title": "GISAID: Global initiative on sharing all influenza data - from vision to reality",
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"year": "2017"
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"year": "2021"
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"article-title": "Enhanced immune evasion of SARS-CoV-2 variants KP.3.1.1 and XEC through N-terminal domain mutations",
"author": "Liu",
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"author": "Li",
"journal-title": "bioRxiv",
"key": "10.1016/j.celrep.2025.115543_bib4",
"year": "2024"
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