Cargando…
COVA1-18 neutralizing antibody protects against SARS-CoV-2 in three preclinical models
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...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Nature Publishing Group UK
2021
|
| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8528857/ https://www.ncbi.nlm.nih.gov/pubmed/34671037 http://dx.doi.org/10.1038/s41467-021-26354-0 |
| _version_ | 1784586340470358016 |
|---|---|
| author | Maisonnasse, Pauline Aldon, Yoann Marc, Aurélien Marlin, Romain Dereuddre-Bosquet, Nathalie Kuzmina, Natalia A. Freyn, Alec W. Snitselaar, Jonne L. Gonçalves, Antonio Caniels, Tom G. Burger, Judith A. Poniman, Meliawati Bontjer, Ilja Chesnais, Virginie Diry, Ségolène Iershov, Anton Ronk, Adam J. Jangra, Sonia Rathnasinghe, Raveen Brouwer, Philip J. M. Bijl, Tom P. L. van Schooten, Jelle Brinkkemper, Mitch Liu, Hejun Yuan, Meng Mire, Chad E. van Breemen, Mariëlle J. Contreras, Vanessa Naninck, Thibaut Lemaître, Julien Kahlaoui, Nidhal Relouzat, Francis Chapon, Catherine Ho Tsong Fang, Raphaël McDanal, Charlene Osei-Twum, Mary St-Amant, Natalie Gagnon, Luc Montefiori, David C. Wilson, Ian A. Ginoux, Eric de Bree, Godelieve J. García-Sastre, Adolfo Schotsaert, Michael Coughlan, Lynda Bukreyev, Alexander van der Werf, Sylvie Guedj, Jérémie Sanders, Rogier W. van Gils, Marit J. Le Grand, Roger |
| author_facet | Maisonnasse, Pauline Aldon, Yoann Marc, Aurélien Marlin, Romain Dereuddre-Bosquet, Nathalie Kuzmina, Natalia A. Freyn, Alec W. Snitselaar, Jonne L. Gonçalves, Antonio Caniels, Tom G. Burger, Judith A. Poniman, Meliawati Bontjer, Ilja Chesnais, Virginie Diry, Ségolène Iershov, Anton Ronk, Adam J. Jangra, Sonia Rathnasinghe, Raveen Brouwer, Philip J. M. Bijl, Tom P. L. van Schooten, Jelle Brinkkemper, Mitch Liu, Hejun Yuan, Meng Mire, Chad E. van Breemen, Mariëlle J. Contreras, Vanessa Naninck, Thibaut Lemaître, Julien Kahlaoui, Nidhal Relouzat, Francis Chapon, Catherine Ho Tsong Fang, Raphaël McDanal, Charlene Osei-Twum, Mary St-Amant, Natalie Gagnon, Luc Montefiori, David C. Wilson, Ian A. Ginoux, Eric de Bree, Godelieve J. García-Sastre, Adolfo Schotsaert, Michael Coughlan, Lynda Bukreyev, Alexander van der Werf, Sylvie Guedj, Jérémie Sanders, Rogier W. van Gils, Marit J. Le Grand, Roger |
| author_sort | Maisonnasse, Pauline |
| collection | PubMed |
| description | 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. |
| format | Online Article Text |
| id | pubmed-8528857 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2021 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-85288572021-10-22 COVA1-18 neutralizing antibody protects against SARS-CoV-2 in three preclinical models Maisonnasse, Pauline Aldon, Yoann Marc, Aurélien Marlin, Romain Dereuddre-Bosquet, Nathalie Kuzmina, Natalia A. Freyn, Alec W. Snitselaar, Jonne L. Gonçalves, Antonio Caniels, Tom G. Burger, Judith A. Poniman, Meliawati Bontjer, Ilja Chesnais, Virginie Diry, Ségolène Iershov, Anton Ronk, Adam J. Jangra, Sonia Rathnasinghe, Raveen Brouwer, Philip J. M. Bijl, Tom P. L. van Schooten, Jelle Brinkkemper, Mitch Liu, Hejun Yuan, Meng Mire, Chad E. van Breemen, Mariëlle J. Contreras, Vanessa Naninck, Thibaut Lemaître, Julien Kahlaoui, Nidhal Relouzat, Francis Chapon, Catherine Ho Tsong Fang, Raphaël McDanal, Charlene Osei-Twum, Mary St-Amant, Natalie Gagnon, Luc Montefiori, David C. Wilson, Ian A. Ginoux, Eric de Bree, Godelieve J. García-Sastre, Adolfo Schotsaert, Michael Coughlan, Lynda Bukreyev, Alexander van der Werf, Sylvie Guedj, Jérémie Sanders, Rogier W. van Gils, Marit J. Le Grand, Roger Nat Commun Article 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. Nature Publishing Group UK 2021-10-20 /pmc/articles/PMC8528857/ /pubmed/34671037 http://dx.doi.org/10.1038/s41467-021-26354-0 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
| spellingShingle | Article Maisonnasse, Pauline Aldon, Yoann Marc, Aurélien Marlin, Romain Dereuddre-Bosquet, Nathalie Kuzmina, Natalia A. Freyn, Alec W. Snitselaar, Jonne L. Gonçalves, Antonio Caniels, Tom G. Burger, Judith A. Poniman, Meliawati Bontjer, Ilja Chesnais, Virginie Diry, Ségolène Iershov, Anton Ronk, Adam J. Jangra, Sonia Rathnasinghe, Raveen Brouwer, Philip J. M. Bijl, Tom P. L. van Schooten, Jelle Brinkkemper, Mitch Liu, Hejun Yuan, Meng Mire, Chad E. van Breemen, Mariëlle J. Contreras, Vanessa Naninck, Thibaut Lemaître, Julien Kahlaoui, Nidhal Relouzat, Francis Chapon, Catherine Ho Tsong Fang, Raphaël McDanal, Charlene Osei-Twum, Mary St-Amant, Natalie Gagnon, Luc Montefiori, David C. Wilson, Ian A. Ginoux, Eric de Bree, Godelieve J. García-Sastre, Adolfo Schotsaert, Michael Coughlan, Lynda Bukreyev, Alexander van der Werf, Sylvie Guedj, Jérémie Sanders, Rogier W. van Gils, Marit J. Le Grand, Roger COVA1-18 neutralizing antibody protects against SARS-CoV-2 in three preclinical models |
| title | COVA1-18 neutralizing antibody protects against SARS-CoV-2 in three preclinical models |
| title_full | COVA1-18 neutralizing antibody protects against SARS-CoV-2 in three preclinical models |
| title_fullStr | COVA1-18 neutralizing antibody protects against SARS-CoV-2 in three preclinical models |
| title_full_unstemmed | COVA1-18 neutralizing antibody protects against SARS-CoV-2 in three preclinical models |
| title_short | COVA1-18 neutralizing antibody protects against SARS-CoV-2 in three preclinical models |
| title_sort | cova1-18 neutralizing antibody protects against sars-cov-2 in three preclinical models |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8528857/ https://www.ncbi.nlm.nih.gov/pubmed/34671037 http://dx.doi.org/10.1038/s41467-021-26354-0 |
| work_keys_str_mv | AT maisonnassepauline cova118neutralizingantibodyprotectsagainstsarscov2inthreepreclinicalmodels AT aldonyoann cova118neutralizingantibodyprotectsagainstsarscov2inthreepreclinicalmodels AT marcaurelien cova118neutralizingantibodyprotectsagainstsarscov2inthreepreclinicalmodels AT marlinromain cova118neutralizingantibodyprotectsagainstsarscov2inthreepreclinicalmodels AT dereuddrebosquetnathalie cova118neutralizingantibodyprotectsagainstsarscov2inthreepreclinicalmodels AT kuzminanataliaa cova118neutralizingantibodyprotectsagainstsarscov2inthreepreclinicalmodels AT freynalecw cova118neutralizingantibodyprotectsagainstsarscov2inthreepreclinicalmodels AT snitselaarjonnel cova118neutralizingantibodyprotectsagainstsarscov2inthreepreclinicalmodels AT goncalvesantonio cova118neutralizingantibodyprotectsagainstsarscov2inthreepreclinicalmodels AT canielstomg cova118neutralizingantibodyprotectsagainstsarscov2inthreepreclinicalmodels AT burgerjuditha cova118neutralizingantibodyprotectsagainstsarscov2inthreepreclinicalmodels AT ponimanmeliawati cova118neutralizingantibodyprotectsagainstsarscov2inthreepreclinicalmodels AT bontjerilja cova118neutralizingantibodyprotectsagainstsarscov2inthreepreclinicalmodels AT chesnaisvirginie cova118neutralizingantibodyprotectsagainstsarscov2inthreepreclinicalmodels AT dirysegolene cova118neutralizingantibodyprotectsagainstsarscov2inthreepreclinicalmodels AT iershovanton cova118neutralizingantibodyprotectsagainstsarscov2inthreepreclinicalmodels AT ronkadamj cova118neutralizingantibodyprotectsagainstsarscov2inthreepreclinicalmodels AT jangrasonia cova118neutralizingantibodyprotectsagainstsarscov2inthreepreclinicalmodels AT rathnasingheraveen cova118neutralizingantibodyprotectsagainstsarscov2inthreepreclinicalmodels AT brouwerphilipjm cova118neutralizingantibodyprotectsagainstsarscov2inthreepreclinicalmodels AT bijltompl cova118neutralizingantibodyprotectsagainstsarscov2inthreepreclinicalmodels AT vanschootenjelle cova118neutralizingantibodyprotectsagainstsarscov2inthreepreclinicalmodels AT brinkkempermitch cova118neutralizingantibodyprotectsagainstsarscov2inthreepreclinicalmodels AT liuhejun cova118neutralizingantibodyprotectsagainstsarscov2inthreepreclinicalmodels AT yuanmeng cova118neutralizingantibodyprotectsagainstsarscov2inthreepreclinicalmodels AT mirechade cova118neutralizingantibodyprotectsagainstsarscov2inthreepreclinicalmodels AT vanbreemenmariellej cova118neutralizingantibodyprotectsagainstsarscov2inthreepreclinicalmodels AT contrerasvanessa cova118neutralizingantibodyprotectsagainstsarscov2inthreepreclinicalmodels AT naninckthibaut cova118neutralizingantibodyprotectsagainstsarscov2inthreepreclinicalmodels AT lemaitrejulien cova118neutralizingantibodyprotectsagainstsarscov2inthreepreclinicalmodels AT kahlaouinidhal cova118neutralizingantibodyprotectsagainstsarscov2inthreepreclinicalmodels AT relouzatfrancis cova118neutralizingantibodyprotectsagainstsarscov2inthreepreclinicalmodels AT chaponcatherine cova118neutralizingantibodyprotectsagainstsarscov2inthreepreclinicalmodels AT hotsongfangraphael cova118neutralizingantibodyprotectsagainstsarscov2inthreepreclinicalmodels AT mcdanalcharlene cova118neutralizingantibodyprotectsagainstsarscov2inthreepreclinicalmodels AT oseitwummary cova118neutralizingantibodyprotectsagainstsarscov2inthreepreclinicalmodels AT stamantnatalie cova118neutralizingantibodyprotectsagainstsarscov2inthreepreclinicalmodels AT gagnonluc cova118neutralizingantibodyprotectsagainstsarscov2inthreepreclinicalmodels AT montefioridavidc cova118neutralizingantibodyprotectsagainstsarscov2inthreepreclinicalmodels AT wilsoniana cova118neutralizingantibodyprotectsagainstsarscov2inthreepreclinicalmodels AT ginouxeric cova118neutralizingantibodyprotectsagainstsarscov2inthreepreclinicalmodels AT debreegodelievej cova118neutralizingantibodyprotectsagainstsarscov2inthreepreclinicalmodels AT garciasastreadolfo cova118neutralizingantibodyprotectsagainstsarscov2inthreepreclinicalmodels AT schotsaertmichael cova118neutralizingantibodyprotectsagainstsarscov2inthreepreclinicalmodels AT coughlanlynda cova118neutralizingantibodyprotectsagainstsarscov2inthreepreclinicalmodels AT bukreyevalexander cova118neutralizingantibodyprotectsagainstsarscov2inthreepreclinicalmodels AT vanderwerfsylvie cova118neutralizingantibodyprotectsagainstsarscov2inthreepreclinicalmodels AT guedjjeremie cova118neutralizingantibodyprotectsagainstsarscov2inthreepreclinicalmodels AT sandersrogierw cova118neutralizingantibodyprotectsagainstsarscov2inthreepreclinicalmodels AT vangilsmaritj cova118neutralizingantibodyprotectsagainstsarscov2inthreepreclinicalmodels AT legrandroger cova118neutralizingantibodyprotectsagainstsarscov2inthreepreclinicalmodels |