ArticleProceedings of the National Academy of Sciences of the United States of America2025
Organoid-based neutralization assays reveal a distinctive profile of SARS-CoV-2 antibodies and recapitulate the real-world efficacy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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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.
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Who cites it
8 citing papers in PubMed.
- Organoid-based evaluation of SA55 and Pemivibart against evolving SARS-CoV-2 variants.Emerging microbes & infections · 2026Article
- Structural and functional characterization of a conserved cryptic epitope on SARS-CoV-2 spike S2 subunit.PLoS pathogens · 2026Article
- Cattle and human organoids reveal 2.3.4.4b H5N1 cross-species transmission potential and neuraminidase-specific neutralizing antibodies in humans.Nature communications · 2026Article
- Human angiotensin‑converting enzyme 2‑specific benzothiazole-based allosteric inhibitor against pan‑sarbecoviruses.Nature communications · 2026Article
- Nasal Epithelial Organoids as Translational Platforms in Inflammatory, Infectious, and Precision Medicine Applications: A Systematic Review.Journal of clinical medicine · 2026Review
- Organoid-Immune Co-Cultures: A Next-Generation approach to disease modeling.Molecular biology reports · 2026Review
- Advances in human respiratory organoid models for studying the pathogenesis and intervention strategies of COVID-19.Virologica Sinica · 2026Review
- Organoid: a promising solution to current challenges in cancer immunotherapy.npj biomedical innovations · 2025Review
Corrections and comments
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Authors and funding
26 authors.
Funding
Abstract
The efficacy of VIR-7831, a class 3 anti-SARS-CoV-2 monoclonal antibody (mAb), was demonstrated repeatedly in clinical trials; yet, reduced neutralization against Omicron variants in cell-line-based neutralization assays led to its withdrawal from clinical use. We developed organoid-based neutralization assays to measure mAb potency. We found that most class 3 mAbs, especially those not blocking receptor-binding domain-ACE2 binding, including VIR-7831, were substantially underestimated in cell-line-based assays. Nasal organoids adequately recapitulated the real-world effectiveness of VIR-7831 because of biologically relevant low ACE2 expression, and exclusively reproduced the in vivo protection of S2 mAbs due to the high TMPRSS2 expression, reminiscent of native human respiratory epithelial cells. Collectively, the robust organoid culture system and biologically relevant expression profiles of ACE2 and TMPRSS2 make nasal organoids present a correlate of in vivo protection of neutralizing mAbs exclusively. The organoid-based neutralization assays, superior to conventional cell-line-based assays, can recapitulate and predict the real-world efficacy of mAbs.
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Registered trials
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.