Evidence map›Paper›PMID 40153503›Full record

ArticleScience advances2025

Preemptive optimization of a clinical antibody for broad neutralization of SARS-CoV-2 variants and robustness against viral escape.

Fangqiang Zhu, Saravanan Rajan, Conor F Hayes, Ka Yin Kwong, Andre R Goncalves, Adam T Zemla, Edmond Y Lau, Yi Zhang, Yingyun Cai, John W Goforth and 35 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Review
  2. Article
  3. Artificial intelligence directed computational protein design: lessons from COVID-19 for pandemic-ready vaccines and antibody therapeutics.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2026
    Review
  4. Article
  5. 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

45 authors.

Fangqiang ZhuBiosciences and Biotechnology Division, Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA.ORCID 0000-0001-6202-2262
Saravanan RajanBiologics Engineering, R&D, AstraZeneca, Gaithersburg, MD 20878, USA.ORCID 0000-0002-5167-4932
Conor F HayesComputational Engineering Division, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA.
Ka Yin KwongBiologics Engineering, R&D, AstraZeneca, Gaithersburg, MD 20878, USA.ORCID 0009-0000-3290-925X
Andre R GoncalvesComputational Engineering Division, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA.ORCID 0000-0002-0320-280X
Adam T ZemlaGlobal Security Computing Applications Division, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA.ORCID 0000-0003-0504-8647
Edmond Y LauBiosciences and Biotechnology Division, Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA.ORCID 0000-0003-0619-7249
Yi ZhangVaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD 20878, USA.ORCID 0000-0002-8228-2560
Yingyun CaiVaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD 20878, USA.ORCID 0000-0002-1101-0920
John W GoforthGlobal Security Computing Applications Division, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA.
Mikel LandajuelaComputational Engineering Division, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA.ORCID 0000-0002-4804-6513
Pavlo GilchukBiologics Engineering, R&D, AstraZeneca, Gaithersburg, MD 20878, USA.
Michael KiernyBiologics Engineering, R&D, AstraZeneca, Gaithersburg, MD 20878, USA.ORCID 0000-0002-5409-0991
Andrew DippelBiologics Engineering, R&D, AstraZeneca, Gaithersburg, MD 20878, USA.ORCID 0000-0003-3453-0803
Bismark AmofahBiologics Engineering, R&D, AstraZeneca, Gaithersburg, MD 20878, USA.ORCID 0009-0001-3663-772X
Gilad KaplanBiologics Engineering, R&D, AstraZeneca, Gaithersburg, MD 20878, USA.ORCID 0000-0003-1374-305X
Vanessa Cadevilla PeanoVaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD 20878, USA.ORCID 0009-0008-8155-6030
Christopher MorehouseVaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD 20878, USA.
Ben SparklinVaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD 20878, USA.ORCID 0000-0002-5547-185X
Vancheswaran GopalakrishnanVaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD 20878, USA.ORCID 0000-0002-8704-035X
Kevin M TuffyVaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD 20878, USA.ORCID 0009-0007-8644-5025
Amy NguyenVaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD 20878, USA.ORCID 0009-0000-9955-9688
Jagadish BeloorVaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD 20878, USA.
Gustavo KijakVaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD 20878, USA.ORCID 0000-0002-2746-9533
Chang LiuChinese Academy of Medical Science (CAMS) Oxford Institute, University of Oxford, Oxford OX3 7BN, UK.
Aiste Dijokaite-GuraliucCentre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK.ORCID 0000-0002-4850-9709
Juthathip MongkolsapayaChinese Academy of Medical Science (CAMS) Oxford Institute, University of Oxford, Oxford OX3 7BN, UK.
Gavin R ScreatonChinese Academy of Medical Science (CAMS) Oxford Institute, University of Oxford, Oxford OX3 7BN, UK.ORCID 0000-0002-3549-4309
Brenden K PetersenComputational Engineering Division, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA.ORCID 0000-0002-1841-3888
Thomas A DesautelsComputational Engineering Division, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA.ORCID 0000-0001-6853-981X
Drew BennettBiosciences and Biotechnology Division, Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA.
Simone ContiBiosciences and Biotechnology Division, Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA.ORCID 0000-0001-7986-567X
Brent W SegelkeBiosciences and Biotechnology Division, Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA.ORCID 0000-0003-3358-5028
Kathryn T ArrildtBiosciences and Biotechnology Division, Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA.
Samantha KaulGlobal Security Computing Applications Division, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA.
Emilia A GrzesiakGlobal Security Computing Applications Division, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA.ORCID 0000-0002-2453-4870
Felipe Leno da SilvaComputational Engineering Division, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA.ORCID 0000-0003-4703-2061
Thomas W BatesComputational Engineering Division, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA.ORCID 0009-0009-4896-7783
Christopher G EarnhartJoint Program Executive Office for Chemical, Biological, Radiological, and Nuclear Defense, US Department of Defense, Frederick, MD 21703, USA.
Svetlana HopkinsJoint Research and Development Inc., Stafford, VA 22556, USA.
Shivshankar SundaramCenter for Bioengineering, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA.ORCID 0000-0001-6675-6765
Mark T EsserVaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD 20878, USA.ORCID 0000-0003-1689-3475
Joseph R FrancicaVaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD 20878, USA.ORCID 0000-0003-1336-4682
Daniel M FaissolComputational Engineering Division, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA.ORCID 0000-0001-6965-983X
LLNL Generative Unconstrained Intelligent Drug Engineering (GUIDE) consortium

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Most previously authorized clinical antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have lost neutralizing activity to recent variants due to rapid viral evolution. To mitigate such escape, we preemptively enhance AZD3152, an antibody authorized for prophylaxis in immunocompromised individuals. Using deep mutational scanning (DMS) on the SARS-CoV-2 antigen, we identify AZD3152 vulnerabilities at antigen positions F456 and D420. Through two iterations of computational antibody design that integrates structure-based modeling, machine-learning, and experimental validation, we co-optimize AZD3152 against 24 contemporary and previous SARS-CoV-2 variants, as well as 20 potential future escape variants. Our top candidate, 3152-1142, restores full potency (100-fold improvement) against the more recently emerged XBB.1.5+F456L variant that escaped AZD3152, maintains potency against previous variants of concern, and shows no additional vulnerability as assessed by DMS. This preemptive mitigation demonstrates a generalizable approach for optimizing existing antibodies against potential future viral escape.

Indexed as

Antibodies, NeutralizingAntibodies, ViralBroadly Neutralizing AntibodiesCOVID-19SARS-CoV-2COVID-19 Drug TreatmentHumansMutationNeutralization TestsSpike Glycoprotein, CoronavirusAntibodies, NeutralizingAntibodies, ViralBroadly Neutralizing AntibodiesSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2

Identifiers

PMID40153503
PMCPMC11952088

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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.