A Novel Human Neutralizing mAb Recognizes Delta, Gamma and Omicron Variants of SARS-CoV-2 and Can Be Used in Combination with Sotrovimab
The dramatic experience with SARS-CoV-2 has alerted the scientific community to be ready to face new epidemics/pandemics caused by new variants. Among the therapies against the pandemic SARS-CoV-2 virus, monoclonal Antibodies (mAbs) targeting the Spike glycoprotein have represented good drugs to int...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/10/5556 |
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| author | Margherita Passariello Veronica Ferrucci Emanuele Sasso Lorenzo Manna Rosa Rapuano Lembo Stefano Pascarella Giovanna Fusco Nicola Zambrano Massimo Zollo Claudia De Lorenzo |
| author_facet | Margherita Passariello Veronica Ferrucci Emanuele Sasso Lorenzo Manna Rosa Rapuano Lembo Stefano Pascarella Giovanna Fusco Nicola Zambrano Massimo Zollo Claudia De Lorenzo |
| author_sort | Margherita Passariello |
| collection | DOAJ |
| description | The dramatic experience with SARS-CoV-2 has alerted the scientific community to be ready to face new epidemics/pandemics caused by new variants. Among the therapies against the pandemic SARS-CoV-2 virus, monoclonal Antibodies (mAbs) targeting the Spike glycoprotein have represented good drugs to interfere in the Spike/ Angiotensin Converting Enzyme-2 (ACE-2) interaction, preventing virus cell entry and subsequent infection, especially in patients with a defective immune system. We obtained, by an innovative phage display selection strategy, specific binders recognizing different epitopes of Spike. The novel human antibodies specifically bind to Spike-Receptor Binding Domain (RBD) in a nanomolar range and interfere in the interaction of Spike with the ACE-2 receptor. We report here that one of these mAbs, named D3, shows neutralizing activity for virus infection in cell cultures by different SARS-CoV-2 variants and retains the ability to recognize the Omicron-derived recombinant RBD differently from the antibodies Casirivimab or Imdevimab. Since anti-Spike mAbs, used individually, might be unable to block the virus cell entry especially in the case of resistant variants, we investigated the possibility to combine D3 with the antibody in clinical use Sotrovimab, and we found that they recognize distinct epitopes and show additive inhibitory effects on the interaction of Omicron-RBD with ACE-2 receptor. Thus, we propose to exploit these mAbs in combinatorial treatments to enhance their potential for both diagnostic and therapeutic applications in the current and future pandemic waves of coronavirus. |
| first_indexed | 2024-03-10T03:44:32Z |
| format | Article |
| id | doaj.art-80e7e43aac304e90a10b58a6b7e3cb11 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T03:44:32Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-80e7e43aac304e90a10b58a6b7e3cb112023-11-23T11:24:35ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-05-012310555610.3390/ijms23105556A Novel Human Neutralizing mAb Recognizes Delta, Gamma and Omicron Variants of SARS-CoV-2 and Can Be Used in Combination with SotrovimabMargherita Passariello0Veronica Ferrucci1Emanuele Sasso2Lorenzo Manna3Rosa Rapuano Lembo4Stefano Pascarella5Giovanna Fusco6Nicola Zambrano7Massimo Zollo8Claudia De Lorenzo9Ceinge—Biotecnologie Avanzate s.c.a.r.l., Via Gaetano Salvatore 486, 80145 Naples, ItalyCeinge—Biotecnologie Avanzate s.c.a.r.l., Via Gaetano Salvatore 486, 80145 Naples, ItalyCeinge—Biotecnologie Avanzate s.c.a.r.l., Via Gaetano Salvatore 486, 80145 Naples, ItalyCeinge—Biotecnologie Avanzate s.c.a.r.l., Via Gaetano Salvatore 486, 80145 Naples, ItalyCeinge—Biotecnologie Avanzate s.c.a.r.l., Via Gaetano Salvatore 486, 80145 Naples, ItalyDepartment of Biochemical Sciences “A. Rossi Fanelli”, Sapienza University of Rome, Viale Regina Elena 332, 00185 Rome, ItalyIstituto Zooprofilattico Sperimentale del Mezzogiorno, Via Salute 2, 80055 Portici Naples, ItalyCeinge—Biotecnologie Avanzate s.c.a.r.l., Via Gaetano Salvatore 486, 80145 Naples, ItalyCeinge—Biotecnologie Avanzate s.c.a.r.l., Via Gaetano Salvatore 486, 80145 Naples, ItalyCeinge—Biotecnologie Avanzate s.c.a.r.l., Via Gaetano Salvatore 486, 80145 Naples, ItalyThe dramatic experience with SARS-CoV-2 has alerted the scientific community to be ready to face new epidemics/pandemics caused by new variants. Among the therapies against the pandemic SARS-CoV-2 virus, monoclonal Antibodies (mAbs) targeting the Spike glycoprotein have represented good drugs to interfere in the Spike/ Angiotensin Converting Enzyme-2 (ACE-2) interaction, preventing virus cell entry and subsequent infection, especially in patients with a defective immune system. We obtained, by an innovative phage display selection strategy, specific binders recognizing different epitopes of Spike. The novel human antibodies specifically bind to Spike-Receptor Binding Domain (RBD) in a nanomolar range and interfere in the interaction of Spike with the ACE-2 receptor. We report here that one of these mAbs, named D3, shows neutralizing activity for virus infection in cell cultures by different SARS-CoV-2 variants and retains the ability to recognize the Omicron-derived recombinant RBD differently from the antibodies Casirivimab or Imdevimab. Since anti-Spike mAbs, used individually, might be unable to block the virus cell entry especially in the case of resistant variants, we investigated the possibility to combine D3 with the antibody in clinical use Sotrovimab, and we found that they recognize distinct epitopes and show additive inhibitory effects on the interaction of Omicron-RBD with ACE-2 receptor. Thus, we propose to exploit these mAbs in combinatorial treatments to enhance their potential for both diagnostic and therapeutic applications in the current and future pandemic waves of coronavirus.https://www.mdpi.com/1422-0067/23/10/5556SARS-CoV-2Omicron variantneutralizing mAbsSpike-RBD/ACE-2combinatorial treatments |
| spellingShingle | Margherita Passariello Veronica Ferrucci Emanuele Sasso Lorenzo Manna Rosa Rapuano Lembo Stefano Pascarella Giovanna Fusco Nicola Zambrano Massimo Zollo Claudia De Lorenzo A Novel Human Neutralizing mAb Recognizes Delta, Gamma and Omicron Variants of SARS-CoV-2 and Can Be Used in Combination with Sotrovimab International Journal of Molecular Sciences SARS-CoV-2 Omicron variant neutralizing mAbs Spike-RBD/ACE-2 combinatorial treatments |
| title | A Novel Human Neutralizing mAb Recognizes Delta, Gamma and Omicron Variants of SARS-CoV-2 and Can Be Used in Combination with Sotrovimab |
| title_full | A Novel Human Neutralizing mAb Recognizes Delta, Gamma and Omicron Variants of SARS-CoV-2 and Can Be Used in Combination with Sotrovimab |
| title_fullStr | A Novel Human Neutralizing mAb Recognizes Delta, Gamma and Omicron Variants of SARS-CoV-2 and Can Be Used in Combination with Sotrovimab |
| title_full_unstemmed | A Novel Human Neutralizing mAb Recognizes Delta, Gamma and Omicron Variants of SARS-CoV-2 and Can Be Used in Combination with Sotrovimab |
| title_short | A Novel Human Neutralizing mAb Recognizes Delta, Gamma and Omicron Variants of SARS-CoV-2 and Can Be Used in Combination with Sotrovimab |
| title_sort | novel human neutralizing mab recognizes delta gamma and omicron variants of sars cov 2 and can be used in combination with sotrovimab |
| topic | SARS-CoV-2 Omicron variant neutralizing mAbs Spike-RBD/ACE-2 combinatorial treatments |
| url | https://www.mdpi.com/1422-0067/23/10/5556 |
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