COVA1-18 neutralizing antibody protects against SARS-CoV-2 in three preclinical models
© 2021. The Author(s)..
Effective treatments against Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) are urgently needed. Monoclonal antibodies have shown promising results in patients. Here, we evaluate the in vivo prophylactic and therapeutic effect of COVA1-18, a neutralizing antibody highly potent against the B.1.1.7 isolate. In both prophylactic and therapeutic settings, SARS-CoV-2 remains undetectable in the lungs of treated hACE2 mice. Therapeutic treatment also causes a reduction in viral loads in the lungs of Syrian hamsters. When administered at 10 mg kg-1 one day prior to a high dose SARS-CoV-2 challenge in cynomolgus macaques, COVA1-18 shows very strong antiviral activity in the upper respiratory compartments. Using a mathematical model, we estimate that COVA1-18 reduces viral infectivity by more than 95% in these compartments, preventing lymphopenia and extensive lung lesions. Our findings demonstrate that COVA1-18 has a strong antiviral activity in three preclinical models and could be a valuable candidate for further clinical evaluation.
| Errataetall: | |
|---|---|
| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
|---|---|
| Enthalten in: |
Nature communications - 12(2021), 1 vom: 20. Okt., Seite 6097 |
| Sprache: |
Englisch |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 02.11.2021 Date Revised 07.12.2022 published: Electronic UpdateOf: Res Sq. 2021 Feb 15;:. - PMID 33619476 Citation Status MEDLINE |
|---|
| doi: |
10.1038/s41467-021-26354-0 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM332112497 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM332112497 | ||
| 003 | DE-627 | ||
| 005 | 20231225214929.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/s41467-021-26354-0 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1107.xml |
| 035 | |a (DE-627)NLM332112497 | ||
| 035 | |a (NLM)34671037 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Maisonnasse, Pauline |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a COVA1-18 neutralizing antibody protects against SARS-CoV-2 in three preclinical models |
| 264 | 1 | |c 2021 | |
| 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 02.11.2021 | ||
| 500 | |a Date Revised 07.12.2022 | ||
| 500 | |a published: Electronic | ||
| 500 | |a UpdateOf: Res Sq. 2021 Feb 15;:. - PMID 33619476 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2021. The Author(s). | ||
| 520 | |a Effective treatments against Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) are urgently needed. Monoclonal antibodies have shown promising results in patients. Here, we evaluate the in vivo prophylactic and therapeutic effect of COVA1-18, a neutralizing antibody highly potent against the B.1.1.7 isolate. In both prophylactic and therapeutic settings, SARS-CoV-2 remains undetectable in the lungs of treated hACE2 mice. Therapeutic treatment also causes a reduction in viral loads in the lungs of Syrian hamsters. When administered at 10 mg kg-1 one day prior to a high dose SARS-CoV-2 challenge in cynomolgus macaques, COVA1-18 shows very strong antiviral activity in the upper respiratory compartments. Using a mathematical model, we estimate that COVA1-18 reduces viral infectivity by more than 95% in these compartments, preventing lymphopenia and extensive lung lesions. Our findings demonstrate that COVA1-18 has a strong antiviral activity in three preclinical models and could be a valuable candidate for further clinical evaluation | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, U.S. Gov't, P.H.S. | |
| 650 | 7 | |a Antibodies, Monoclonal |2 NLM | |
| 650 | 7 | |a Antibodies, Neutralizing |2 NLM | |
| 650 | 7 | |a Antiviral Agents |2 NLM | |
| 650 | 7 | |a COVA1-18 |2 NLM | |
| 650 | 7 | |a ACE2 protein, human |2 NLM | |
| 650 | 7 | |a EC 3.4.17.23 |2 NLM | |
| 650 | 7 | |a Angiotensin-Converting Enzyme 2 |2 NLM | |
| 650 | 7 | |a EC 3.4.17.23 |2 NLM | |
| 700 | 1 | |a Aldon, Yoann |e verfasserin |4 aut | |
| 700 | 1 | |a Marc, Aurélien |e verfasserin |4 aut | |
| 700 | 1 | |a Marlin, Romain |e verfasserin |4 aut | |
| 700 | 1 | |a Dereuddre-Bosquet, Nathalie |e verfasserin |4 aut | |
| 700 | 1 | |a Kuzmina, Natalia A |e verfasserin |4 aut | |
| 700 | 1 | |a Freyn, Alec W |e verfasserin |4 aut | |
| 700 | 1 | |a Snitselaar, Jonne L |e verfasserin |4 aut | |
| 700 | 1 | |a Gonçalves, Antonio |e verfasserin |4 aut | |
| 700 | 1 | |a Caniels, Tom G |e verfasserin |4 aut | |
| 700 | 1 | |a Burger, Judith A |e verfasserin |4 aut | |
| 700 | 1 | |a Poniman, Meliawati |e verfasserin |4 aut | |
| 700 | 1 | |a Bontjer, Ilja |e verfasserin |4 aut | |
| 700 | 1 | |a Chesnais, Virginie |e verfasserin |4 aut | |
| 700 | 1 | |a Diry, Ségolène |e verfasserin |4 aut | |
| 700 | 1 | |a Iershov, Anton |e verfasserin |4 aut | |
| 700 | 1 | |a Ronk, Adam J |e verfasserin |4 aut | |
| 700 | 1 | |a Jangra, Sonia |e verfasserin |4 aut | |
| 700 | 1 | |a Rathnasinghe, Raveen |e verfasserin |4 aut | |
| 700 | 1 | |a Brouwer, Philip J M |e verfasserin |4 aut | |
| 700 | 1 | |a Bijl, Tom P L |e verfasserin |4 aut | |
| 700 | 1 | |a van Schooten, Jelle |e verfasserin |4 aut | |
| 700 | 1 | |a Brinkkemper, Mitch |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Hejun |e verfasserin |4 aut | |
| 700 | 1 | |a Yuan, Meng |e verfasserin |4 aut | |
| 700 | 1 | |a Mire, Chad E |e verfasserin |4 aut | |
| 700 | 1 | |a van Breemen, Mariëlle J |e verfasserin |4 aut | |
| 700 | 1 | |a Contreras, Vanessa |e verfasserin |4 aut | |
| 700 | 1 | |a Naninck, Thibaut |e verfasserin |4 aut | |
| 700 | 1 | |a Lemaître, Julien |e verfasserin |4 aut | |
| 700 | 1 | |a Kahlaoui, Nidhal |e verfasserin |4 aut | |
| 700 | 1 | |a Relouzat, Francis |e verfasserin |4 aut | |
| 700 | 1 | |a Chapon, Catherine |e verfasserin |4 aut | |
| 700 | 1 | |a Ho Tsong Fang, Raphaël |e verfasserin |4 aut | |
| 700 | 1 | |a McDanal, Charlene |e verfasserin |4 aut | |
| 700 | 1 | |a Osei-Twum, Mary |e verfasserin |4 aut | |
| 700 | 1 | |a St-Amant, Natalie |e verfasserin |4 aut | |
| 700 | 1 | |a Gagnon, Luc |e verfasserin |4 aut | |
| 700 | 1 | |a Montefiori, David C |e verfasserin |4 aut | |
| 700 | 1 | |a Wilson, Ian A |e verfasserin |4 aut | |
| 700 | 1 | |a Ginoux, Eric |e verfasserin |4 aut | |
| 700 | 1 | |a de Bree, Godelieve J |e verfasserin |4 aut | |
| 700 | 1 | |a García-Sastre, Adolfo |e verfasserin |4 aut | |
| 700 | 1 | |a Schotsaert, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Coughlan, Lynda |e verfasserin |4 aut | |
| 700 | 1 | |a Bukreyev, Alexander |e verfasserin |4 aut | |
| 700 | 1 | |a van der Werf, Sylvie |e verfasserin |4 aut | |
| 700 | 1 | |a Guedj, Jérémie |e verfasserin |4 aut | |
| 700 | 1 | |a Sanders, Rogier W |e verfasserin |4 aut | |
| 700 | 1 | |a van Gils, Marit J |e verfasserin |4 aut | |
| 700 | 1 | |a Le Grand, Roger |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Nature communications |d 2010 |g 12(2021), 1 vom: 20. Okt., Seite 6097 |w (DE-627)NLM199274525 |x 2041-1723 |7 nnns |
| 773 | 1 | 8 | |g volume:12 |g year:2021 |g number:1 |g day:20 |g month:10 |g pages:6097 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1038/s41467-021-26354-0 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 12 |j 2021 |e 1 |b 20 |c 10 |h 6097 | ||