SARS-CoV-2 hijacks neutralizing dimeric IgA for nasal infection and injury in Syrian hamsters1
Prevention 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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
|---|---|
| Enthalten in: |
Emerging microbes & infections - 12(2023), 2 vom: 04. Dez., Seite 2245921 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Zhou, Biao [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 23.08.2023 Date Revised 24.08.2023 published: Print Citation Status MEDLINE |
|---|
| doi: |
10.1080/22221751.2023.2245921 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM360420818 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM360420818 | ||
| 003 | DE-627 | ||
| 005 | 20231226082957.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1080/22221751.2023.2245921 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1201.xml |
| 035 | |a (DE-627)NLM360420818 | ||
| 035 | |a (NLM)37542391 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Zhou, Biao |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a SARS-CoV-2 hijacks neutralizing dimeric IgA for nasal infection and injury in Syrian hamsters1 |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 23.08.2023 | ||
| 500 | |a Date Revised 24.08.2023 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Prevention 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a IgA | |
| 650 | 4 | |a SARS-CoV-2 | |
| 650 | 4 | |a antibody-mediated trans-infection | |
| 650 | 4 | |a nasal turbinate | |
| 650 | 4 | |a neutralizing antibody | |
| 650 | 7 | |a Antibodies, Viral |2 NLM | |
| 650 | 7 | |a Antibodies, Neutralizing |2 NLM | |
| 650 | 7 | |a Immunoglobulin A |2 NLM | |
| 650 | 7 | |a Spike Glycoprotein, Coronavirus |2 NLM | |
| 650 | 7 | |a spike protein, SARS-CoV-2 |2 NLM | |
| 700 | 1 | |a Zhou, Runhong |e verfasserin |4 aut | |
| 700 | 1 | |a Chan, Jasper Fuk-Woo |e verfasserin |4 aut | |
| 700 | 1 | |a Zeng, Jianwei |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Qi |e verfasserin |4 aut | |
| 700 | 1 | |a Yuan, Shuofeng |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Li |e verfasserin |4 aut | |
| 700 | 1 | |a Robinot, Rémy |e verfasserin |4 aut | |
| 700 | 1 | |a Shan, Sisi |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Na |e verfasserin |4 aut | |
| 700 | 1 | |a Ge, Jiwan |e verfasserin |4 aut | |
| 700 | 1 | |a Kwong, Hugo Yat-Hei |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Dongyan |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Haoran |e verfasserin |4 aut | |
| 700 | 1 | |a Chan, Chris Chung-Sing |e verfasserin |4 aut | |
| 700 | 1 | |a Poon, Vincent Kwok-Man |e verfasserin |4 aut | |
| 700 | 1 | |a Chu, Hin |e verfasserin |4 aut | |
| 700 | 1 | |a Yue, Ming |e verfasserin |4 aut | |
| 700 | 1 | |a Kwan, Ka-Yi |e verfasserin |4 aut | |
| 700 | 1 | |a Chan, Chun-Yin |e verfasserin |4 aut | |
| 700 | 1 | |a Chan, Chris Chun-Yiu |e verfasserin |4 aut | |
| 700 | 1 | |a Chik, Kenn Ka-Heng |e verfasserin |4 aut | |
| 700 | 1 | |a Du, Zhenglong |e verfasserin |4 aut | |
| 700 | 1 | |a Au, Ka-Kit |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Haode |e verfasserin |4 aut | |
| 700 | 1 | |a Man, Hiu-On |e verfasserin |4 aut | |
| 700 | 1 | |a Cao, Jianli |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Cun |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Ziyi |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Jie |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Youqiang |e verfasserin |4 aut | |
| 700 | 1 | |a Yeung, Man-Lung |e verfasserin |4 aut | |
| 700 | 1 | |a To, Kelvin Kai-Wang |e verfasserin |4 aut | |
| 700 | 1 | |a Ho, David D |e verfasserin |4 aut | |
| 700 | 1 | |a Chakrabarti, Lisa A |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xinquan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Linqi |e verfasserin |4 aut | |
| 700 | 1 | |a Yuen, Kwok-Yung |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Zhiwei |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Emerging microbes & infections |d 2012 |g 12(2023), 2 vom: 04. Dez., Seite 2245921 |w (DE-627)NLM249608804 |x 2222-1751 |7 nnns |
| 773 | 1 | 8 | |g volume:12 |g year:2023 |g number:2 |g day:04 |g month:12 |g pages:2245921 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1080/22221751.2023.2245921 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 12 |j 2023 |e 2 |b 04 |c 12 |h 2245921 | ||