Recombinant neutralizing secretory IgA antibodies for preventing mucosal acquisition and transmission of SARS-CoV-2
Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved..
Passive delivery of antibodies to mucosal sites may be a valuable adjunct to COVID-19 vaccination to prevent infection, treat viral carriage, or block transmission. Neutralizing monoclonal IgG antibodies are already approved for systemic delivery, and several clinical trials have been reported for delivery to mucosal sites where SARS-CoV-2 resides and replicates in early infection. However, secretory IgA may be preferred because the polymeric complex is adapted for the harsh, unstable external mucosal environment. Here, we investigated the feasibility of producing neutralizing monoclonal IgA antibodies against SARS-CoV-2. We engineered two class-switched mAbs that express well as monomeric and secretory IgA (SIgA) variants with high antigen-binding affinities and increased stability in mucosal secretions compared to their IgG counterparts. SIgAs had stronger virus neutralization activities than IgG mAbs and were protective against SARS-CoV-2 infection in an in vivo murine model. Furthermore, SIgA1 can be aerosolized for topical delivery using a mesh nebulizer. Our findings provide a persuasive case for developing recombinant SIgAs for mucosal application as a new tool in the fight against COVID-19.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:32 |
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| Enthalten in: |
Molecular therapy : the journal of the American Society of Gene Therapy - 32(2024), 3 vom: 06. März, Seite 689-703 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Göritzer, Kathrin [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 11.03.2024 Date Revised 15.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ymthe.2024.01.025 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM367586142 |
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| 100 | 1 | |a Göritzer, Kathrin |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Recombinant neutralizing secretory IgA antibodies for preventing mucosal acquisition and transmission of SARS-CoV-2 |
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| 520 | |a Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a Passive delivery of antibodies to mucosal sites may be a valuable adjunct to COVID-19 vaccination to prevent infection, treat viral carriage, or block transmission. Neutralizing monoclonal IgG antibodies are already approved for systemic delivery, and several clinical trials have been reported for delivery to mucosal sites where SARS-CoV-2 resides and replicates in early infection. However, secretory IgA may be preferred because the polymeric complex is adapted for the harsh, unstable external mucosal environment. Here, we investigated the feasibility of producing neutralizing monoclonal IgA antibodies against SARS-CoV-2. We engineered two class-switched mAbs that express well as monomeric and secretory IgA (SIgA) variants with high antigen-binding affinities and increased stability in mucosal secretions compared to their IgG counterparts. SIgAs had stronger virus neutralization activities than IgG mAbs and were protective against SARS-CoV-2 infection in an in vivo murine model. Furthermore, SIgA1 can be aerosolized for topical delivery using a mesh nebulizer. Our findings provide a persuasive case for developing recombinant SIgAs for mucosal application as a new tool in the fight against COVID-19 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Nicotiana benthamiana | |
| 650 | 4 | |a SARS-CoV-2 | |
| 650 | 4 | |a molecular pharming | |
| 650 | 4 | |a monoclonal antibodies | |
| 650 | 4 | |a mucosal antibodies | |
| 650 | 4 | |a passive immunization | |
| 650 | 4 | |a secretory IgA | |
| 650 | 4 | |a topical delivery | |
| 650 | 4 | |a virus neutralization | |
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| 650 | 7 | |a Antibodies, Monoclonal |2 NLM | |
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| 700 | 1 | |a Groppelli, Elisabetta |e verfasserin |4 aut | |
| 700 | 1 | |a Grünwald-Gruber, Clemens |e verfasserin |4 aut | |
| 700 | 1 | |a Figl, Rudolf |e verfasserin |4 aut | |
| 700 | 1 | |a Ni, Fengfeng |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Huimin |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Yuncheng |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Yalan |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Qinxue |e verfasserin |4 aut | |
| 700 | 1 | |a Puligedda, Rama Devudu |e verfasserin |4 aut | |
| 700 | 1 | |a Jung, Jae-Wan |e verfasserin |4 aut | |
| 700 | 1 | |a Strasser, Richard |e verfasserin |4 aut | |
| 700 | 1 | |a Dessain, Scott |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Julian K-C |e verfasserin |4 aut | |
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