Journal
CELL HOST & MICROBE
Volume 29, Issue 4, Pages 551-+Publisher
CELL PRESS
DOI: 10.1016/j.chom.2021.02.019
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Funding
- Research Grants Council Collaborative Research Fund [C7156-20G]
- University Development Fund from the University of Hong Kong
- Li Ka Shing Faculty of Medicine Matching Fund from the University of Hong Kong
- Innovation and Technology Fund
- Innovation and Technology Commission
- Hong Kong Special Administrative Region Government
- National Program on Key Research Project of China [2020YFA0707500, 2020YFA0707504]
- Shaw Foundation Hong Kong
- Lee Wan Keung Charity Foundation Limited
- Hui Hoy and Chow Sin Lan Charity Fund Limited
- Chan Yin Chuen Memorial Charitable Foundation
- Hong Kong Hainan Commercial Association South China Microbiology Research Fund
- Jessie AMP
- George Ho Charitable Foundation
- Perfect Shape Medical Limited
- Foo Oi Foundation Limited
- Lo Ying Shek Chi Wai Foundation
- Theme-Based Research Scheme [T11-706/18-N]
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Human neutralizing antibodies demonstrated effective inhibition of SARS-CoV-2 infection in the lungs but were less effective in nasal turbinates, indicating implications for subprotection, reinfection, and vaccine development.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized by a burst in the upper respiratory portal for high transmissibility. To determine human neutralizing antibodies (HuNAbs) for entry protection, we tested three potent HuNAbs (IC50 range, 0.0007-0.35 mu g/mL) against live SARS-CoV-2 infection in the golden Syrian hamster model. These HuNAbs inhibit SARS-CoV-2 infection by competing with human angiotensin converting enzyme-2 for binding to the viral receptor binding domain (RBD). Prophylactic intraperitoneal or intranasal injection of individual HuNAb or DNA vaccination significantly reduces infection in the lungs but not in the nasal turbinates of hamsters intranasally challenged with SARS-CoV-2. Although postchallenge HuNAb therapy suppresses viral loads and lung damage, robust infection is observed in nasal turbinates treated within 1-3 days. Our findings demonstrate that systemic HuNAb suppresses SARS-CoV-2 replication and injury in lungs; however, robust viral infection in nasal turbinate may outcompete the antibody with significant implications to subprotection, reinfection, and vaccine.
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