Glyco engineered pentameric SARS-CoV-2 IgMs show superior activities compared to IgG1 orthologues
Copyright © 2023 Kallolimath, Palt, Föderl-Höbenreich, Sun, Chen, Pruckner, Eidenberger, Strasser, Zatloukal and Steinkellner..
Immunoglobulin M (IgM) is the largest antibody isotype with unique features like extensive glycosylation and oligomerization. Major hurdles in characterizing its properties are difficulties in the production of well-defined multimers. Here we report the expression of two SARS-CoV-2 neutralizing monoclonal antibodies in glycoengineered plants. Isotype switch from IgG1 to IgM resulted in the production of IgMs, composed of 21 human protein subunits correctly assembled into pentamers. All four recombinant monoclonal antibodies carried a highly reproducible human-type N-glycosylation profile, with a single dominant N-glycan species at each glycosite. Both pentameric IgMs exhibited increased antigen binding and virus neutralization potency, up to 390-fold, compared to the parental IgG1. Collectively, the results may impact on the future design of vaccines, diagnostics and antibody-based therapies and emphasize the versatile use of plants for the expression of highly complex human proteins with targeted posttranslational modifications.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
|---|---|
| Enthalten in: |
Frontiers in immunology - 14(2023) vom: 04., Seite 1147960 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Kallolimath, Somanath [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 28.06.2023 Date Revised 01.07.2023 published: Electronic-eCollection Citation Status MEDLINE |
|---|
| doi: |
10.3389/fimmu.2023.1147960 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM358609194 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM358609194 | ||
| 003 | DE-627 | ||
| 005 | 20231226210541.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3389/fimmu.2023.1147960 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1195.xml |
| 035 | |a (DE-627)NLM358609194 | ||
| 035 | |a (NLM)37359564 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Kallolimath, Somanath |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Glyco engineered pentameric SARS-CoV-2 IgMs show superior activities compared to IgG1 orthologues |
| 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 28.06.2023 | ||
| 500 | |a Date Revised 01.07.2023 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 Kallolimath, Palt, Föderl-Höbenreich, Sun, Chen, Pruckner, Eidenberger, Strasser, Zatloukal and Steinkellner. | ||
| 520 | |a Immunoglobulin M (IgM) is the largest antibody isotype with unique features like extensive glycosylation and oligomerization. Major hurdles in characterizing its properties are difficulties in the production of well-defined multimers. Here we report the expression of two SARS-CoV-2 neutralizing monoclonal antibodies in glycoengineered plants. Isotype switch from IgG1 to IgM resulted in the production of IgMs, composed of 21 human protein subunits correctly assembled into pentamers. All four recombinant monoclonal antibodies carried a highly reproducible human-type N-glycosylation profile, with a single dominant N-glycan species at each glycosite. Both pentameric IgMs exhibited increased antigen binding and virus neutralization potency, up to 390-fold, compared to the parental IgG1. Collectively, the results may impact on the future design of vaccines, diagnostics and antibody-based therapies and emphasize the versatile use of plants for the expression of highly complex human proteins with targeted posttranslational modifications | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a SARS-CoV-2 | |
| 650 | 4 | |a glycosylation | |
| 650 | 4 | |a monoclonal antibodies | |
| 650 | 4 | |a pentameric IgM | |
| 650 | 4 | |a plant expression | |
| 650 | 7 | |a Immunoglobulin G |2 NLM | |
| 650 | 7 | |a Antibodies, Viral |2 NLM | |
| 650 | 7 | |a Immunoglobulin M |2 NLM | |
| 650 | 7 | |a Antibodies, Monoclonal |2 NLM | |
| 650 | 7 | |a Recombinant Proteins |2 NLM | |
| 700 | 1 | |a Palt, Roman |e verfasserin |4 aut | |
| 700 | 1 | |a Föderl-Höbenreich, Esther |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Lin |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Qiang |e verfasserin |4 aut | |
| 700 | 1 | |a Pruckner, Florian |e verfasserin |4 aut | |
| 700 | 1 | |a Eidenberger, Lukas |e verfasserin |4 aut | |
| 700 | 1 | |a Strasser, Richard |e verfasserin |4 aut | |
| 700 | 1 | |a Zatloukal, Kurt |e verfasserin |4 aut | |
| 700 | 1 | |a Steinkellner, Herta |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Frontiers in immunology |d 2010 |g 14(2023) vom: 04., Seite 1147960 |w (DE-627)NLM215811453 |x 1664-3224 |7 nnns |
| 773 | 1 | 8 | |g volume:14 |g year:2023 |g day:04 |g pages:1147960 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.3389/fimmu.2023.1147960 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 14 |j 2023 |b 04 |h 1147960 | ||