Susceptibility of SARS-CoV-2 Omicron Variants to Therapeutic Monoclonal Antibodies: Systematic Review and Meta-analysis
ABSTRACT SARS-CoV-2 Omicron variants contain many mutations in its spike receptor-binding domain, the target of all authorized monoclonal antibodies (MAbs). Determining the extent to which Omicron variants reduced MAb susceptibility is critical to preventing and treating COVID-19. We systematically...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2022-08-01
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| Series: | Microbiology Spectrum |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.00926-22 |
| _version_ | 1811338028097994752 |
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| author | Kaiming Tao Philip L. Tzou Sergei L. Kosakovsky Pond John P. A. Ioannidis Robert W. Shafer |
| author_facet | Kaiming Tao Philip L. Tzou Sergei L. Kosakovsky Pond John P. A. Ioannidis Robert W. Shafer |
| author_sort | Kaiming Tao |
| collection | DOAJ |
| description | ABSTRACT SARS-CoV-2 Omicron variants contain many mutations in its spike receptor-binding domain, the target of all authorized monoclonal antibodies (MAbs). Determining the extent to which Omicron variants reduced MAb susceptibility is critical to preventing and treating COVID-19. We systematically reviewed PubMed and three preprint servers, last updated 11 April 2022, for the in vitro activity of authorized MAbs against the Omicron variants. Fifty-one studies were eligible, including 50 containing Omicron BA.1 susceptibility data and 17 containing Omicron BA.2 susceptibility data. The first two authorized MAb combinations, bamlanivimab/etesevimab and casirivimab/imdevimab, were largely inactive against the Omicron BA.1 and BA.2 variants. In 34 studies, sotrovimab displayed a median 4.0-fold (interquartile range [IQR]: 2.6 to 6.9) reduction in activity against Omicron BA.1, and in 12 studies, it displayed a median 17-fold (IQR: 13 to 30) reduction in activity against Omicron BA.2. In 15 studies, the combination cilgavimab/tixagevimab displayed a median 86-fold (IQR: 27 to 151) reduction in activity against Omicron BA.1, and in six studies, it displayed a median 5.4-fold (IQR: 3.7 to 6.9) reduction in activity against Omicron BA.2. In eight studies against Omicron BA.1 and six studies against Omicron BA.2, bebtelovimab displayed no reduction in activity. Disparate results between assays were common. For authorized MAbs, 51/268 (19.0%) results for wild-type control variants and 78/348 (22.4%) results for Omicron BA.1 and BA.2 variants were more than 4-fold below or 4-fold above the median result for that MAb. Highly disparate results between published assays indicate a need for improved MAb susceptibility test standardization or interassay calibration. IMPORTANCE Monoclonal antibodies (MAbs) targeting the SARS-CoV-2 spike protein are among the most effective measures for preventing and treating COVID-19. However, SARS-CoV-2 Omicron variants contain many mutations in their spike receptor-binding domains, the target of all authorized MAbs. Therefore, determining the extent to which Omicron variants reduced MAb susceptibility is critical to preventing and treating COVID-19. We identified 51 studies that reported the in vitro susceptibility of the two main Omicron variants BA.1 and BA.2 to therapeutic MAbs in advanced clinical development, including eight authorized individual MAbs and three authorized MAb combinations. We estimated the degree to which different MAbs displayed reduced activity against Omicron variants. The marked loss of activity of many MAbs against Omicron variants underscores the importance of developing MAbs that target conserved regions of spike. Highly disparate results between assays indicate the need for improved MAb susceptibility test standardization. |
| first_indexed | 2024-04-13T18:03:54Z |
| format | Article |
| id | doaj.art-b8a461e8a712480b863faa163a6ba332 |
| institution | Directory Open Access Journal |
| issn | 2165-0497 |
| language | English |
| last_indexed | 2024-04-13T18:03:54Z |
| publishDate | 2022-08-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj.art-b8a461e8a712480b863faa163a6ba3322022-12-22T02:36:08ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972022-08-0110410.1128/spectrum.00926-22Susceptibility of SARS-CoV-2 Omicron Variants to Therapeutic Monoclonal Antibodies: Systematic Review and Meta-analysisKaiming Tao0Philip L. Tzou1Sergei L. Kosakovsky Pond2John P. A. Ioannidis3Robert W. Shafer4Division of Infectious Diseases, Department of Medicine, Stanford University, Stanford, California, USADivision of Infectious Diseases, Department of Medicine, Stanford University, Stanford, California, USAInstitute for Genomics and Evolutionary Medicine, Temple University, Philadelphia, Pennsylvania, USADepartments of Medicine and of Epidemiology and Population Health and Meta-Research Innovation Center at Stanford (METRICS), Stanford University, Stanford, California, USADivision of Infectious Diseases, Department of Medicine, Stanford University, Stanford, California, USAABSTRACT SARS-CoV-2 Omicron variants contain many mutations in its spike receptor-binding domain, the target of all authorized monoclonal antibodies (MAbs). Determining the extent to which Omicron variants reduced MAb susceptibility is critical to preventing and treating COVID-19. We systematically reviewed PubMed and three preprint servers, last updated 11 April 2022, for the in vitro activity of authorized MAbs against the Omicron variants. Fifty-one studies were eligible, including 50 containing Omicron BA.1 susceptibility data and 17 containing Omicron BA.2 susceptibility data. The first two authorized MAb combinations, bamlanivimab/etesevimab and casirivimab/imdevimab, were largely inactive against the Omicron BA.1 and BA.2 variants. In 34 studies, sotrovimab displayed a median 4.0-fold (interquartile range [IQR]: 2.6 to 6.9) reduction in activity against Omicron BA.1, and in 12 studies, it displayed a median 17-fold (IQR: 13 to 30) reduction in activity against Omicron BA.2. In 15 studies, the combination cilgavimab/tixagevimab displayed a median 86-fold (IQR: 27 to 151) reduction in activity against Omicron BA.1, and in six studies, it displayed a median 5.4-fold (IQR: 3.7 to 6.9) reduction in activity against Omicron BA.2. In eight studies against Omicron BA.1 and six studies against Omicron BA.2, bebtelovimab displayed no reduction in activity. Disparate results between assays were common. For authorized MAbs, 51/268 (19.0%) results for wild-type control variants and 78/348 (22.4%) results for Omicron BA.1 and BA.2 variants were more than 4-fold below or 4-fold above the median result for that MAb. Highly disparate results between published assays indicate a need for improved MAb susceptibility test standardization or interassay calibration. IMPORTANCE Monoclonal antibodies (MAbs) targeting the SARS-CoV-2 spike protein are among the most effective measures for preventing and treating COVID-19. However, SARS-CoV-2 Omicron variants contain many mutations in their spike receptor-binding domains, the target of all authorized MAbs. Therefore, determining the extent to which Omicron variants reduced MAb susceptibility is critical to preventing and treating COVID-19. We identified 51 studies that reported the in vitro susceptibility of the two main Omicron variants BA.1 and BA.2 to therapeutic MAbs in advanced clinical development, including eight authorized individual MAbs and three authorized MAb combinations. We estimated the degree to which different MAbs displayed reduced activity against Omicron variants. The marked loss of activity of many MAbs against Omicron variants underscores the importance of developing MAbs that target conserved regions of spike. Highly disparate results between assays indicate the need for improved MAb susceptibility test standardization.https://journals.asm.org/doi/10.1128/spectrum.00926-22SARS-CoV-2Omicron variantmonoclonal antibodyneutralizationspike proteinCOVID-19 |
| spellingShingle | Kaiming Tao Philip L. Tzou Sergei L. Kosakovsky Pond John P. A. Ioannidis Robert W. Shafer Susceptibility of SARS-CoV-2 Omicron Variants to Therapeutic Monoclonal Antibodies: Systematic Review and Meta-analysis Microbiology Spectrum SARS-CoV-2 Omicron variant monoclonal antibody neutralization spike protein COVID-19 |
| title | Susceptibility of SARS-CoV-2 Omicron Variants to Therapeutic Monoclonal Antibodies: Systematic Review and Meta-analysis |
| title_full | Susceptibility of SARS-CoV-2 Omicron Variants to Therapeutic Monoclonal Antibodies: Systematic Review and Meta-analysis |
| title_fullStr | Susceptibility of SARS-CoV-2 Omicron Variants to Therapeutic Monoclonal Antibodies: Systematic Review and Meta-analysis |
| title_full_unstemmed | Susceptibility of SARS-CoV-2 Omicron Variants to Therapeutic Monoclonal Antibodies: Systematic Review and Meta-analysis |
| title_short | Susceptibility of SARS-CoV-2 Omicron Variants to Therapeutic Monoclonal Antibodies: Systematic Review and Meta-analysis |
| title_sort | susceptibility of sars cov 2 omicron variants to therapeutic monoclonal antibodies systematic review and meta analysis |
| topic | SARS-CoV-2 Omicron variant monoclonal antibody neutralization spike protein COVID-19 |
| url | https://journals.asm.org/doi/10.1128/spectrum.00926-22 |
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