An Engineered Antibody with Broad Protective Efficacy in Murine Models of SARS and COVID-19
The recurrent zoonotic spillover of coronaviruses (CoVs) into the human population underscores the need for broadly active countermeasures. Here, we employed a directed evolution approach to engineer three SARS-CoV-2 antibodies for enhanced neutralization breadth and potency. One of the affinity-matured variants, ADG-2, displays strong binding activity to a large panel of sarbecovirus receptor binding domains (RBDs) and neutralizes representative epidemic sarbecoviruses with remarkable potency. Structural and biochemical studies demonstrate that ADG-2 employs a unique angle of approach to recognize a highly conserved epitope overlapping the receptor binding site. In murine models of SARS-CoV and SARS-CoV-2 infection, passive transfer of ADG-2 provided complete protection against respiratory burden, viral replication in the lungs, and lung pathology. Altogether, ADG-2 represents a promising broad-spectrum therapeutic candidate for the treatment and prevention of SARS-CoV-2 and future emerging SARS-like CoVs.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2020 |
|---|---|
| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2020 |
|---|---|
| Enthalten in: |
bioRxiv : the preprint server for biology - (2020) vom: 17. Nov. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Rappazzo, C Garrett [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
|---|
| Anmerkungen: |
Date Revised 19.10.2023 published: Electronic Citation Status PubMed-not-MEDLINE |
|---|
| doi: |
10.1101/2020.11.17.385500 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM318027119 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM318027119 | ||
| 003 | DE-627 | ||
| 005 | 20231225164510.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2020 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1101/2020.11.17.385500 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1060.xml |
| 035 | |a (DE-627)NLM318027119 | ||
| 035 | |a (NLM)33236009 | ||
| 035 | |a (PII)2020.11.17.385500 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Rappazzo, C Garrett |e verfasserin |4 aut | |
| 245 | 1 | 3 | |a An Engineered Antibody with Broad Protective Efficacy in Murine Models of SARS and COVID-19 |
| 264 | 1 | |c 2020 | |
| 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 Revised 19.10.2023 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a The recurrent zoonotic spillover of coronaviruses (CoVs) into the human population underscores the need for broadly active countermeasures. Here, we employed a directed evolution approach to engineer three SARS-CoV-2 antibodies for enhanced neutralization breadth and potency. One of the affinity-matured variants, ADG-2, displays strong binding activity to a large panel of sarbecovirus receptor binding domains (RBDs) and neutralizes representative epidemic sarbecoviruses with remarkable potency. Structural and biochemical studies demonstrate that ADG-2 employs a unique angle of approach to recognize a highly conserved epitope overlapping the receptor binding site. In murine models of SARS-CoV and SARS-CoV-2 infection, passive transfer of ADG-2 provided complete protection against respiratory burden, viral replication in the lungs, and lung pathology. Altogether, ADG-2 represents a promising broad-spectrum therapeutic candidate for the treatment and prevention of SARS-CoV-2 and future emerging SARS-like CoVs | ||
| 650 | 4 | |a Preprint | |
| 700 | 1 | |a Tse, Longping V |e verfasserin |4 aut | |
| 700 | 1 | |a Kaku, Chengzi I |e verfasserin |4 aut | |
| 700 | 1 | |a Wrapp, Daniel |e verfasserin |4 aut | |
| 700 | 1 | |a Sakharkar, Mrunal |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Deli |e verfasserin |4 aut | |
| 700 | 1 | |a Deveau, Laura M |e verfasserin |4 aut | |
| 700 | 1 | |a Yockachonis, Thomas J |e verfasserin |4 aut | |
| 700 | 1 | |a Herbert, Andrew S |e verfasserin |4 aut | |
| 700 | 1 | |a Battles, Michael B |e verfasserin |4 aut | |
| 700 | 1 | |a O'Brien, Cecilia M |e verfasserin |4 aut | |
| 700 | 1 | |a Brown, Michael E |e verfasserin |4 aut | |
| 700 | 1 | |a Geoghegan, James C |e verfasserin |4 aut | |
| 700 | 1 | |a Belk, Jonathan |e verfasserin |4 aut | |
| 700 | 1 | |a Peng, Linghang |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Linlin |e verfasserin |4 aut | |
| 700 | 1 | |a Scobey, Trevor D |e verfasserin |4 aut | |
| 700 | 1 | |a Burton, Dennis R |e verfasserin |4 aut | |
| 700 | 1 | |a Nemazee, David |e verfasserin |4 aut | |
| 700 | 1 | |a Dye, John M |e verfasserin |4 aut | |
| 700 | 1 | |a Voss, James E |e verfasserin |4 aut | |
| 700 | 1 | |a Gunn, Bronwyn M |e verfasserin |4 aut | |
| 700 | 1 | |a McLellan, Jason S |e verfasserin |4 aut | |
| 700 | 1 | |a Baric, Ralph S |e verfasserin |4 aut | |
| 700 | 1 | |a Gralinski, Lisa E |e verfasserin |4 aut | |
| 700 | 1 | |a Walker, Laura M |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t bioRxiv : the preprint server for biology |d 2020 |g (2020) vom: 17. Nov. |w (DE-627)NLM31090014X |7 nnns |
| 773 | 1 | 8 | |g year:2020 |g day:17 |g month:11 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1101/2020.11.17.385500 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |j 2020 |b 17 |c 11 | ||