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Record W4385606768 · doi:10.1080/22221751.2023.2245921

SARS-CoV-2 hijacks neutralizing dimeric IgA for nasal infection and injury in Syrian hamsters <sup>1</sup>

2023· article· en· W4385606768 on OpenAlexaff
Biao Zhou, Runhong Zhou, Jasper Fuk‐Woo Chan, Jianwei Zeng, Qi Zhang, Shuofeng Yuan, Li Liu, Rémy Robinot, Sisi Shan, Na Liu, Jiwan Ge, Hugo Yat-Hei Kwong, Dongyan Zhou, Haoran Xu, Chris Chung‐Sing Chan, Vincent Kwok‐Man Poon, Hin Chu, Ming Yue, Ka‐Yi Kwan, Chun-Yin Chan, Chris Chun-Yiu Chan, Kenn Ka‐Heng Chik, Zhenglong Du, Ka‐Kit Au, Haode Huang, Hiu-On Man, Jianli Cao, Cun Li, Ziyi Wang, Jie Zhou, You‐Qiang Song, Man Lung Yeung, Kelvin Kai‐Wang To, David D. Ho, Lisa A. Chakrabarti, Xinquan Wang, Linqi Zhang, Kwok‐Yung Yuen, Zhiwei Chen

Bibliographic record

VenueEmerging Microbes & Infections · 2023
Typearticle
Languageen
FieldMedicine
TopicSARS-CoV-2 and COVID-19 Research
Canadian institutionsColumbia CollegeCanadian Nautical Research Society
FundersHealth and Medical Research FundInnovation and Technology FundFood and Health BureauWellcome Trust
KeywordsVirologyBiologyAntibodyNeutralizing antibodyVero cellMedicineImmunologyVirus

Abstract

fetched live from OpenAlex

evaluation of IgA neutralizing antibodies. Here, we report the efficacy of receptor binding domain (RBD)-specific monomeric B8-mIgA1 and B8-mIgA2, and dimeric B8-dIgA1, B8-dIgA2 and TH335-dIgA1 against intranasal SARS-CoV-2 challenge in Syrian hamsters. These antibodies exhibited comparable neutralization potency against authentic virus by competing with human angiotensin converting enzyme-2 (ACE2) receptor for RBD binding. While reducing viral loads in lungs significantly, prophylactic intranasal B8-dIgA unexpectedly led to high amount of infectious viruses and extended damage in NT compared to controls. Mechanistically, B8-dIgA failed to inhibit SARS-CoV-2 cell-to-cell transmission, but was hijacked by the virus through dendritic cell-mediated trans-infection of NT epithelia leading to robust nasal infection. Cryo-EM further revealed B8 as a class II antibody binding trimeric RBDs in 3-up or 2-up/1-down conformation. Neutralizing dIgA, therefore, may engage an unexpected mode of SARS-CoV-2 nasal infection and injury.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.606
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.002
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.037
GPT teacher head0.358
Teacher spread0.321 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations15
Published2023
Admission routes1
Has abstractyes

Explore more

Same venueEmerging Microbes & InfectionsSame topicSARS-CoV-2 and COVID-19 ResearchFrench-language works237,207