期刊
SCIENCE
卷 374, 期 6566, 页码 472-+出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.abh2315
关键词
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资金
- Overton family for this urgent study (Coronavirus Immunotherapeutic Consortium), COVID-19 Therapeutics Accelerator [INV-006133]
- Bill and Melinda Gates Foundation [OPP1210938]
- GHR Foundation (Coronavirus Immunotherapeutic Consortium)
- NIH/NIAID [U19 AI142790-S1]
- Emergent Ventures at the Mercatus Center, George Mason University
- Early Postdoc Mobility Fellowship of the Swiss Translating Duke Health Immunology Initiative
- Bill and Melinda Gates Foundation [INV-006133, OPP1210938] Funding Source: Bill and Melinda Gates Foundation
Antibody-based therapeutics and vaccines are crucial in combating COVID-19, especially with mutations and transmission of SARS-CoV-2. An international consortium identified multiple RBD-directed antibody communities, providing a framework for selecting treatment cocktails.
Antibody-based therapeutics and vaccines are essential to combat COVID-19 morbidity and mortality after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Multiple mutations in SARS-CoV-2 that could impair antibody defenses propagated in human-to-human transmission and spillover or spillback events between humans and animals. To develop prevention and therapeutic strategies, we formed an international consortium to map the epitope landscape on the SARS-CoV-2 spike protein, defining and structurally illustrating seven receptor binding domain (RBD)-directed antibody communities with distinct footprints and competition profiles. Pseudovirion-based neutralization assays reveal spike mutations, individually and clustered together in variants, that affect antibody function among the communities. Key classes of RBD-targeted antibodies maintain neutralization activity against these emerging SARS-CoV-2 variants. These results provide a framework for selecting antibody treatment cocktails and understanding how viral variants might affect antibody therapeutic efficacy.
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