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)00688-1
Earle, Ambrosino, Fiore-Gartland, Goldblatt, Gilbert et al., Evidence for antibody as a protective correlate for COVID-19 vaccines, Vaccine,
doi:10.1016/j.vaccine.2021.05.063
Feng, 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.adg7404
Li, 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:10.1101/2024.11.12.623078
Liu, Wang, Nair, Yu, Rapp et al., Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike, Nature,
doi:10.1038/s41586-020-2571-7
Liu, Yu, Jian, Yang, Song et al., Enhanced immune evasion of SARS-CoV-2 KP.3.1.1 and XEC through NTD glycosylation,
doi:10.1101/2024.10.23.619754
Liu, 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)00738-2
Simon, Kota, Bloomquist, Hanley, Forgacs et al., PARIS and SPARTA: Finding the Achilles' Heel of SARS-CoV-2, mSphere,
doi:10.1128/msphere.00179-22
Smith, Lapedes, De Jong, Bestebroer, Rimmelzwaan et al., Mapping the antigenic and genetic evolution of influenza virus, Science,
doi:10.1126/science.1097211
Uriu, 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:10.1101/2024.11.20.624471
Wang, 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.2024.01.014
Wang, Guo, Ho, Ho, Activity of Research-Grade Pemivibart against Recent SARS-CoV-2 JN.1 Sublineages, N. Engl. J. Med,
doi:10.1056/NEJMc2410203
Wang, 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.2022.12.018
Wang, 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:10.1080/22221751.2024.2402880
Wang, 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)00058-1
Wang, 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.2022.04.003
Zhang, 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.2024.06.028
DOI record:
{
"DOI": "10.1016/j.celrep.2025.115543",
"ISSN": [
"2211-1247"
],
"URL": "http://dx.doi.org/10.1016/j.celrep.2025.115543",
"alternative-id": [
"S2211124725003146"
],
"article-number": "115543",
"assertion": [
{
"label": "This article is maintained by",
"name": "publisher",
"value": "Elsevier"
},
{
"label": "Article Title",
"name": "articletitle",
"value": "Antibody evasiveness of SARS-CoV-2 subvariants KP.3.1.1 and XEC"
},
{
"label": "Journal Title",
"name": "journaltitle",
"value": "Cell Reports"
},
{
"label": "CrossRef DOI link to publisher maintained version",
"name": "articlelink",
"value": "https://doi.org/10.1016/j.celrep.2025.115543"
},
{
"label": "Content Type",
"name": "content_type",
"value": "article"
},
{
"label": "Copyright",
"name": "copyright",
"value": "© 2025 The Author(s). Published by Elsevier Inc."
}
],
"author": [
{
"affiliation": [],
"family": "Wang",
"given": "Qian",
"sequence": "first"
},
{
"affiliation": [],
"family": "Guo",
"given": "Yicheng",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Mellis",
"given": "Ian A.",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Wu",
"given": "Madeline",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Mohri",
"given": "Hiroshi",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Gherasim",
"given": "Carmen",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Valdez",
"given": "Riccardo",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Purpura",
"given": "Lawrence J.",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Yin",
"given": "Michael T.",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Gordon",
"given": "Aubree",
"sequence": "additional"
},
{
"ORCID": "https://orcid.org/0000-0003-1627-149X",
"affiliation": [],
"authenticated-orcid": false,
"family": "Ho",
"given": "David D.",
"sequence": "additional"
}
],
"container-title": "Cell Reports",
"container-title-short": "Cell Reports",
"content-domain": {
"crossmark-restriction": true,
"domain": [
"cell.com",
"elsevier.com",
"sciencedirect.com"
]
},
"created": {
"date-parts": [
[
2025,
4,
8
]
],
"date-time": "2025-04-08T21:25:16Z",
"timestamp": 1744147516000
},
"deposited": {
"date-parts": [
[
2025,
4,
22
]
],
"date-time": "2025-04-22T16:02:55Z",
"timestamp": 1745337775000
},
"funder": [
{
"DOI": "10.13039/100000865",
"doi-asserted-by": "publisher",
"id": [
{
"asserted-by": "publisher",
"id": "10.13039/100000865",
"id-type": "DOI"
}
],
"name": "Gates Foundation"
},
{
"DOI": "10.13039/100000002",
"doi-asserted-by": "publisher",
"id": [
{
"asserted-by": "publisher",
"id": "10.13039/100000002",
"id-type": "DOI"
}
],
"name": "NIH"
},
{
"DOI": "10.13039/100006474",
"doi-asserted-by": "publisher",
"id": [
{
"asserted-by": "publisher",
"id": "10.13039/100006474",
"id-type": "DOI"
}
],
"name": "Columbia University"
}
],
"indexed": {
"date-parts": [
[
2025,
4,
22
]
],
"date-time": "2025-04-22T16:40:06Z",
"timestamp": 1745340006003,
"version": "3.40.4"
},
"is-referenced-by-count": 0,
"issue": "4",
"issued": {
"date-parts": [
[
2025,
4
]
]
},
"journal-issue": {
"issue": "4",
"published-print": {
"date-parts": [
[
2025,
4
]
]
}
},
"language": "en",
"license": [
{
"URL": "https://www.elsevier.com/tdm/userlicense/1.0/",
"content-version": "tdm",
"delay-in-days": 0,
"start": {
"date-parts": [
[
2025,
4,
1
]
],
"date-time": "2025-04-01T00:00:00Z",
"timestamp": 1743465600000
}
},
{
"URL": "https://www.elsevier.com/legal/tdmrep-license",
"content-version": "tdm",
"delay-in-days": 0,
"start": {
"date-parts": [
[
2025,
4,
1
]
],
"date-time": "2025-04-01T00:00:00Z",
"timestamp": 1743465600000
}
},
{
"URL": "http://creativecommons.org/licenses/by/4.0/",
"content-version": "vor",
"delay-in-days": 0,
"start": {
"date-parts": [
[
2025,
3,
19
]
],
"date-time": "2025-03-19T00:00:00Z",
"timestamp": 1742342400000
}
}
],
"link": [
{
"URL": "https://api.elsevier.com/content/article/PII:S2211124725003146?httpAccept=text/xml",
"content-type": "text/xml",
"content-version": "vor",
"intended-application": "text-mining"
},
{
"URL": "https://api.elsevier.com/content/article/PII:S2211124725003146?httpAccept=text/plain",
"content-type": "text/plain",
"content-version": "vor",
"intended-application": "text-mining"
}
],
"member": "78",
"original-title": [],
"page": "115543",
"prefix": "10.1016",
"published": {
"date-parts": [
[
2025,
4
]
]
},
"published-print": {
"date-parts": [
[
2025,
4
]
]
},
"publisher": "Elsevier BV",
"reference": [
{
"DOI": "10.2807/1560-7917.ES.2017.22.13.30494",
"article-title": "GISAID: Global initiative on sharing all influenza data - from vision to reality",
"author": "Shu",
"doi-asserted-by": "crossref",
"journal-title": "Euro Surveill.",
"key": "10.1016/j.celrep.2025.115543_bib1",
"volume": "22",
"year": "2017"
},
{
"DOI": "10.1016/j.vaccine.2021.05.063",
"article-title": "Evidence for antibody as a protective correlate for COVID-19 vaccines",
"author": "Earle",
"doi-asserted-by": "crossref",
"first-page": "4423",
"journal-title": "Vaccine",
"key": "10.1016/j.celrep.2025.115543_bib2",
"volume": "39",
"year": "2021"
},
{
"DOI": "10.1016/S1473-3099(24)00738-2",
"article-title": "Enhanced immune evasion of SARS-CoV-2 variants KP.3.1.1 and XEC through N-terminal domain mutations",
"author": "Liu",
"doi-asserted-by": "crossref",
"first-page": "e6",
"journal-title": "Lancet Infect. Dis.",
"key": "10.1016/j.celrep.2025.115543_bib3",
"volume": "25",
"year": "2025"
},
{
"article-title": "Immune Evasion, Cell-Cell Fusion, and Spike Stability of the SARS-CoV-2 XEC Variant: Role of Glycosylation Mutations at the N-terminal Domain",
"author": "Li",
"journal-title": "bioRxiv",
"key": "10.1016/j.celrep.2025.115543_bib4",
"year": "2024"
},
{
"DOI": "10.1016/j.immuni.2022.04.003",
"article-title": "Analysis of memory B cells identifies conserved neutralizing epitopes on the N-terminal domain of variant SARS-Cov-2 spike proteins",
"author": "Wang",
"doi-asserted-by": "crossref",
"first-page": "998",
"journal-title": "Immunity",
"key": "10.1016/j.celrep.2025.115543_bib5",
"volume": "55",
"year": "2022"
},
{
"key": "10.1016/j.celrep.2025.115543_bib6",
"unstructured": "FDA (2024). FDA Roundup: March 22, 2024. https://www.fda.gov/news-events/press-announcements/fda-roundup-march-22-2024."
},
{
"DOI": "10.1126/scitranslmed.adg7404",
"article-title": "Broadly neutralizing antibodies against sarbecoviruses generated by immunization of macaques with an AS03-adjuvanted COVID-19 vaccine",
"author": "Feng",
"doi-asserted-by": "crossref",
"journal-title": "Sci. Transl. Med.",
"key": "10.1016/j.celrep.2025.115543_bib7",
"volume": "15",
"year": "2023"
},
{
"DOI": "10.1016/j.molcel.2024.06.028",
"article-title": "SARS-CoV-2 Omicron XBB lineage spike structures, conformations, antigenicity, and receptor recognition",
"author": "Zhang",
"doi-asserted-by": "crossref",
"first-page": "2747",
"journal-title": "Mol. Cell",
"key": "10.1016/j.celrep.2025.115543_bib8",
"volume": "84",
"year": "2024"
},
{
"article-title": "Enhanced immune evasion of SARS-CoV-2 KP.3.1.1 and XEC through NTD glycosylation",
"author": "Liu",
"journal-title": "bioRxiv",
"key": "10.1016/j.celrep.2025.115543_bib9",
"year": "2024"
},
{
"article-title": "Neutralizing antibody evasion of SARS-CoV-2 JN.1 derivatives KP.3, KP.3.1.1, LB.1, and XEC",
"author": "Sano",
"journal-title": "bioRxiv",
"key": "10.1016/j.celrep.2025.115543_bib10",
"year": "2024"
},
{
"DOI": "10.1016/S1473-3099(24)00688-1",
"article-title": "Impact of JN.1 booster vaccination on neutralisation of SARS-CoV-2 variants KP.3.1.1 and XEC",
"author": "Arora",
"doi-asserted-by": "crossref",
"first-page": "e732",
"journal-title": "Lancet Infect. Dis.",
"key": "10.1016/j.celrep.2025.115543_bib11",
"volume": "24",
"year": "2024"
},
{
"article-title": "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",
"author": "Uriu",
"journal-title": "bioRxiv",
"key": "10.1016/j.celrep.2025.115543_bib12",
"year": "2024"
},
{
"DOI": "10.1056/NEJMc2410203",
"article-title": "Activity of Research-Grade Pemivibart against Recent SARS-CoV-2 JN.1 Sublineages",
"author": "Wang",
"doi-asserted-by": "crossref",
"first-page": "1863",
"journal-title": "N. Engl. J. Med.",
"key": "10.1016/j.celrep.2025.115543_bib13",
"volume": "391",
"year": "2024"
},
{
"DOI": "10.1080/22221751.2024.2402880",
"article-title": "Recurrent SARS-CoV-2 spike mutations confer growth advantages to select JN.1 sublineages",
"author": "Wang",
"doi-asserted-by": "crossref",
"journal-title": "Emerg. Microb. Infect.",
"key": "10.1016/j.celrep.2025.115543_bib14",
"volume": "13",
"year": "2024"
},
{
"DOI": "10.1016/S1473-3099(25)00058-1",
"article-title": "KP.2-based monovalent mRNA vaccines robustly boost antibody responses to SARS-CoV-2",
"author": "Wang",
"doi-asserted-by": "crossref",
"first-page": "e133",
"journal-title": "Lancet Infect. Dis.",
"key": "10.1016/j.celrep.2025.115543_bib15",
"volume": "25",
"year": "2025"
},
{
"DOI": "10.1016/j.chom.2024.01.014",
"article-title": "XBB.1.5 monovalent mRNA vaccine booster elicits robust neutralizing antibodies against XBB subvariants and JN.1",
"author": "Wang",
"doi-asserted-by": "crossref",
"first-page": "315",
"journal-title": "Cell Host Microbe",
"key": "10.1016/j.celrep.2025.115543_bib16",
"volume": "32",
"year": "2024"
},
{
"DOI": "10.1126/science.1097211",
"article-title": "Mapping the antigenic and genetic evolution of influenza virus",
"author": "Smith",
"doi-asserted-by": "crossref",
"first-page": "371",
"journal-title": "Science",
"key": "10.1016/j.celrep.2025.115543_bib17",
"volume": "305",
"year": "2004"
},
{
"DOI": "10.1128/msphere.00179-22",
"article-title": "PARIS and SPARTA: Finding the Achilles' Heel of SARS-CoV-2",
"author": "Simon",
"doi-asserted-by": "crossref",
"journal-title": "mSphere",
"key": "10.1016/j.celrep.2025.115543_bib18",
"volume": "7",
"year": "2022"
},
{
"DOI": "10.1038/s41586-020-2571-7",
"article-title": "Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike",
"author": "Liu",
"doi-asserted-by": "crossref",
"first-page": "450",
"journal-title": "Nature",
"key": "10.1016/j.celrep.2025.115543_bib19",
"volume": "584",
"year": "2020"
},
{
"DOI": "10.1038/s41586-023-06750-w",
"article-title": "Antigenicity and receptor affinity of SARS-CoV-2 BA.2.86 spike",
"author": "Wang",
"doi-asserted-by": "crossref",
"first-page": "639",
"journal-title": "Nature",
"key": "10.1016/j.celrep.2025.115543_bib20",
"volume": "624",
"year": "2023"
},
{
"DOI": "10.1038/s41586-022-05053-w",
"article-title": "Antibody evasion by SARS-CoV-2 Omicron subvariants BA.2.12.1, BA.4 and BA.5",
"author": "Wang",
"doi-asserted-by": "crossref",
"first-page": "603",
"journal-title": "Nature",
"key": "10.1016/j.celrep.2025.115543_bib21",
"volume": "608",
"year": "2022"
},
{
"DOI": "10.1016/j.cell.2022.12.018",
"article-title": "Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants",
"author": "Wang",
"doi-asserted-by": "crossref",
"first-page": "279",
"journal-title": "Cellule",
"key": "10.1016/j.celrep.2025.115543_bib22",
"volume": "186",
"year": "2023"
}
],
"reference-count": 22,
"references-count": 22,
"relation": {},
"resource": {
"primary": {
"URL": "https://linkinghub.elsevier.com/retrieve/pii/S2211124725003146"
}
},
"score": 1,
"short-title": [],
"source": "Crossref",
"subject": [],
"subtitle": [],
"title": "Antibody evasiveness of SARS-CoV-2 subvariants KP.3.1.1 and XEC",
"type": "journal-article",
"update-policy": "https://doi.org/10.1016/elsevier_cm_policy",
"volume": "44"
}