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SARS-CoV-2 spike in complex with the ZB8 neutralizing antibody Fab (3U)
Structural highlights
Publication Abstract from PubMedPrevention of robust severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in nasal turbinate (NT) requires in vivo 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. SARS-CoV-2 hijacks neutralizing dimeric IgA for nasal infection and injury in Syrian hamsters(1).,Zhou B, Zhou R, Chan JF, Zeng J, Zhang Q, Yuan S, Liu L, Robinot R, Shan S, Liu N, Ge J, Kwong HY, Zhou D, Xu H, Chan CC, Poon VK, Chu H, Yue M, Kwan KY, Chan CY, Chan CC, Chik KK, Du Z, Au KK, Huang H, Man HO, Cao J, Li C, Wang Z, Zhou J, Song Y, Yeung ML, To KK, Ho DD, Chakrabarti LA, Wang X, Zhang L, Yuen KY, Chen Z Emerg Microbes Infect. 2023 Dec;12(2):2245921. doi: , 10.1080/22221751.2023.2245921. PMID:37542391[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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