Evidence map›Paper›PMID 39827186›Full record

ArticleNature communications2025

Reverse mutational scanning of SARS-CoV-2 spike BA.2.86 identifies epitopes contributing to immune escape from polyclonal sera.

Najat Bdeir, Tatjana Lüddecke, Henrike Maaß, Stefan Schmelz, Ulfert Rand, Henning Jacobsen, Kristin Metzdorf, Upasana Kulkarni, Anne Cossmann, Metodi V Stankov and 6 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed.

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  13. Antigenic cartography using variant-specific hamster sera reveals substantial antigenic variation among Omicron subvariants.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Najat BdeirDepartment of Viral Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Tatjana LüddeckeDepartment of Viral Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Henrike MaaßDepartment of Viral Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.ORCID http://orcid.org/0000-0002-4654-5423
Stefan SchmelzDepartment Structure and Function of Proteins, Helmholtz Centre for Infection Research Braunschweig, Braunschweig, Germany.
Ulfert RandDSMZ- German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany.ORCID http://orcid.org/0000-0002-5946-4921
Henning JacobsenDepartment of Viral Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.ORCID http://orcid.org/0000-0002-7831-1330
Kristin MetzdorfDepartment of Viral Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Upasana KulkarniDepartment of Viral Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Anne CossmannDepartment of Rheumatology and Immunology, Hannover Medical School, Hannover, Germany.
Metodi V StankovDepartment of Rheumatology and Immunology, Hannover Medical School, Hannover, Germany.ORCID http://orcid.org/0000-0003-3001-2478
Markus HoffmannInfection Biology Unit, German Primate Center - Leibniz Institute for Primate Research, Göttingen, Germany.ORCID http://orcid.org/0000-0003-4603-7696
Stefan PöhlmannInfection Biology Unit, German Primate Center - Leibniz Institute for Primate Research, Göttingen, Germany.ORCID http://orcid.org/0000-0001-6086-9136
Wulf BlankenfeldtDepartment Structure and Function of Proteins, Helmholtz Centre for Infection Research Braunschweig, Braunschweig, Germany.ORCID http://orcid.org/0000-0001-9886-9668
Alexandra Dopfer-JablonkaDepartment of Rheumatology and Immunology, Hannover Medical School, Hannover, Germany.ORCID http://orcid.org/0000-0001-7129-100X
Georg M N Behrens *Department of Rheumatology and Immunology, Hannover Medical School, Hannover, Germany.ORCID http://orcid.org/0000-0003-3111-621X
Luka Čičin-Šain *Department of Viral Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany. Luka.Cicin-Sain@helmholtz-hzi.de.ORCID http://orcid.org/0000-0003-3978-778X

Funding

Deutsche Forschungsgemeinschaft (German Research Foundation) FOR2830
6 · The paper itself

Abstract

The recently detected Omicron BA.2.86 lineage contains more than 30 amino acid mutations relative to BA.2. BA.2.86 and its JN.1 derivative evade neutralization by serum antibodies of fully vaccinated individuals. In this study, we elucidate epitopes driving the immune escape of BA.2.86 and JN.1 via pseudovirus neutralization. Here we generate 33 BA.2.86 mutants, each reverting a single mutation back to BA.2. We use this library in an approach that we call reverse mutational scanning to define distinct neutralization titers against each epitope. Mutations within the receptor binding domain at K356T, V483Δ, and to a lesser extent N460K, A484K, and F486P enhance immune escape. Interestingly, 16insMPLF within the spike N-terminal domain and P621S within S1/S2 also significantly contribute to antibody escape of BA.2.86. Upon XBB.1.5 booster vaccination, neutralization titers against JN.1 and BA.2.86 improve considerably, and residual immune escape is driven by 16insMPLF, N460K, E554K, and to a lesser extent P621S, and A484K.

Indexed as

Antibodies, ViralCOVID-19EpitopesImmune EvasionSARS-CoV-2Spike Glycoprotein, CoronavirusAntibodies, NeutralizingHumansMutationNeutralization TestsAntibodies, NeutralizingAntibodies, ViralEpitopesSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2

Identifiers

PMID39827186
PMCPMC11743207

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.