Etesevimab in combination with JS026 neutralizing SARS-CoV-2 and its variants
The neutralizing antibody is a potential therapeutic for the ongoing COVID-19 pandemic. As an antiviral agent, numerous mAbs recognize the epitopes that overlap with ACE2-binding sites in the SARS-CoV-2-RBD. Some studies have shown that residual changes on the spike protein can significantly decreas...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2022-12-01
|
| Series: | Emerging Microbes and Infections |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/22221751.2022.2032374 |
| _version_ | 1818323812613095424 |
|---|---|
| author | Fengze Wang Li Li Yang Dou Rui Shi Xiaomin Duan Hongchuan Liu Jing Zhang DanDan Liu Jing Wu Yang He Jun Lan Bai Lu Hui Feng Jinghua Yan |
| author_facet | Fengze Wang Li Li Yang Dou Rui Shi Xiaomin Duan Hongchuan Liu Jing Zhang DanDan Liu Jing Wu Yang He Jun Lan Bai Lu Hui Feng Jinghua Yan |
| author_sort | Fengze Wang |
| collection | DOAJ |
| description | The neutralizing antibody is a potential therapeutic for the ongoing COVID-19 pandemic. As an antiviral agent, numerous mAbs recognize the epitopes that overlap with ACE2-binding sites in the SARS-CoV-2-RBD. Some studies have shown that residual changes on the spike protein can significantly decrease the efficiency of neutralizing antibodies. To address this issue, a therapeutic cocktail could be an effective countermeasure. In the present study, we isolated a fully human neutralizing antibody, JS026, from a convalescent patient. The comparative analysis revealed that JS026 binding to SARS-CoV-2-RBD mainly located between epitopes for class 2 and class 3 mAbs as opposed to that of class 1 (etesevimab) antibodies. A cocktail of etesevimab and JS026 increased neutralizing efficacy against both wild-type SARS-CoV-2 and the recent emergence of Alpha, Beta, Gamma, and Delta variants. JS026 and the cocktail reduced virus titers in the infected lungs of hACE2 transgenic mice and relieved pathological changes. These findings would benefit antibody-based therapeutic countermeasures in the treatment of COVID-19. |
| first_indexed | 2024-12-13T11:18:38Z |
| format | Article |
| id | doaj.art-6c4076ee56804353bcf7166d10f6e8fa |
| institution | Directory Open Access Journal |
| issn | 2222-1751 |
| language | English |
| last_indexed | 2024-12-13T11:18:38Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj.art-6c4076ee56804353bcf7166d10f6e8fa2022-12-21T23:48:34ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512022-12-0111154855110.1080/22221751.2022.20323742032374Etesevimab in combination with JS026 neutralizing SARS-CoV-2 and its variantsFengze Wang0Li Li1Yang Dou2Rui Shi3Xiaomin Duan4Hongchuan Liu5Jing Zhang6DanDan Liu7Jing Wu8Yang He9Jun Lan10Bai Lu11Hui Feng12Jinghua Yan13Institute of Microbiology, Chinese Academy of SciencesShanghai Junshi Biosciences Co. LtdIDG/McGovern Institute for Brain Research, Tsinghua UniversityInstitute of Microbiology, Chinese Academy of SciencesInstitute of Microbiology, Chinese Academy of SciencesShanghai Junshi Biosciences Co. LtdShanghai Junshi Biosciences Co. LtdShanghai Junshi Biosciences Co. LtdShanghai Junshi Biosciences Co. LtdShanghai Junshi Biosciences Co. LtdTsinghua UniversityIDG/McGovern Institute for Brain Research, Tsinghua UniversityShanghai Junshi Biosciences Co. LtdInstitute of Microbiology, Chinese Academy of SciencesThe neutralizing antibody is a potential therapeutic for the ongoing COVID-19 pandemic. As an antiviral agent, numerous mAbs recognize the epitopes that overlap with ACE2-binding sites in the SARS-CoV-2-RBD. Some studies have shown that residual changes on the spike protein can significantly decrease the efficiency of neutralizing antibodies. To address this issue, a therapeutic cocktail could be an effective countermeasure. In the present study, we isolated a fully human neutralizing antibody, JS026, from a convalescent patient. The comparative analysis revealed that JS026 binding to SARS-CoV-2-RBD mainly located between epitopes for class 2 and class 3 mAbs as opposed to that of class 1 (etesevimab) antibodies. A cocktail of etesevimab and JS026 increased neutralizing efficacy against both wild-type SARS-CoV-2 and the recent emergence of Alpha, Beta, Gamma, and Delta variants. JS026 and the cocktail reduced virus titers in the infected lungs of hACE2 transgenic mice and relieved pathological changes. These findings would benefit antibody-based therapeutic countermeasures in the treatment of COVID-19.http://dx.doi.org/10.1080/22221751.2022.2032374sars-cov-2etesevimabjs026antibody cocktailvariants of concern |
| spellingShingle | Fengze Wang Li Li Yang Dou Rui Shi Xiaomin Duan Hongchuan Liu Jing Zhang DanDan Liu Jing Wu Yang He Jun Lan Bai Lu Hui Feng Jinghua Yan Etesevimab in combination with JS026 neutralizing SARS-CoV-2 and its variants Emerging Microbes and Infections sars-cov-2 etesevimab js026 antibody cocktail variants of concern |
| title | Etesevimab in combination with JS026 neutralizing SARS-CoV-2 and its variants |
| title_full | Etesevimab in combination with JS026 neutralizing SARS-CoV-2 and its variants |
| title_fullStr | Etesevimab in combination with JS026 neutralizing SARS-CoV-2 and its variants |
| title_full_unstemmed | Etesevimab in combination with JS026 neutralizing SARS-CoV-2 and its variants |
| title_short | Etesevimab in combination with JS026 neutralizing SARS-CoV-2 and its variants |
| title_sort | etesevimab in combination with js026 neutralizing sars cov 2 and its variants |
| topic | sars-cov-2 etesevimab js026 antibody cocktail variants of concern |
| url | http://dx.doi.org/10.1080/22221751.2022.2032374 |
| work_keys_str_mv | AT fengzewang etesevimabincombinationwithjs026neutralizingsarscov2anditsvariants AT lili etesevimabincombinationwithjs026neutralizingsarscov2anditsvariants AT yangdou etesevimabincombinationwithjs026neutralizingsarscov2anditsvariants AT ruishi etesevimabincombinationwithjs026neutralizingsarscov2anditsvariants AT xiaominduan etesevimabincombinationwithjs026neutralizingsarscov2anditsvariants AT hongchuanliu etesevimabincombinationwithjs026neutralizingsarscov2anditsvariants AT jingzhang etesevimabincombinationwithjs026neutralizingsarscov2anditsvariants AT dandanliu etesevimabincombinationwithjs026neutralizingsarscov2anditsvariants AT jingwu etesevimabincombinationwithjs026neutralizingsarscov2anditsvariants AT yanghe etesevimabincombinationwithjs026neutralizingsarscov2anditsvariants AT junlan etesevimabincombinationwithjs026neutralizingsarscov2anditsvariants AT bailu etesevimabincombinationwithjs026neutralizingsarscov2anditsvariants AT huifeng etesevimabincombinationwithjs026neutralizingsarscov2anditsvariants AT jinghuayan etesevimabincombinationwithjs026neutralizingsarscov2anditsvariants |