Robust SARS-CoV-2 Infection in Nasal Turbinate Despite Systemic Neutralizing Antibody

SARS-CoV-2 is characterized by a burst in upper-respiratory portal for high transmissibility. To determine human neutralizing antibodies (HuNAbs) for entry protection, we generated HuNAbs that bind to conformational determinants of viral receptor binding domain (RBD). HuNAb ZDY20 prevented pseudovirus and live virus entry with IC 90 values of 1.24 µg/ml and 1 µg/ml, respectively, by competing with human cellular receptor ACE2 for RBD binding. Prophylactic intraperitoneal injection of 10 mg/ml ZDY20 significantly reduced infection in lungs but not nasal turbinate of hamsters intranasally-challenged with SARS-CoV-2. Although post-challenge ZDY20 therapy suppressed viral loads and lung damage, robust infection was found in nasal turbinate treated within 1-3 days. Our findings demonstrated that systemic HuNAb suppresses SARS-CoV-2 replication and lung injury, yet insufficient entry blockade may implicate vaccine sub-protection and re-infection. Funding: This study was partly supported by University Development Fund and Li Ka Shing Faculty of Medicine Matching Fund from HKU to AIDS Institute, Health@InnoHK (Centre for Virology, Vaccinology and Therapeutics), Innovation and Technology Commission, HKSAR of China; and donations of Lo Ying Shek Chi Wai Foundation, Richard Yu and Carol Yu, the Shaw Foundation of Hong Kong, Michael Seak-Kan Tong, May Tam Mak Mei Yin, Hui Ming, Hui Hoy and Chow Sin Lan Charity Fund Limited, Chan Yin Chuen Memorial Charitable Foundation, Marina Man-Wai Lee, the Hong Kong Hainan Commercial Association South China Microbiology Research Fund, the Jessie & George Ho Charitable Foundation, Perfect Shape Medical Limited, Kai Chong Tong, Foo Oi Foundation Limited, and Tse Kam Ming Laurence. ZC’s team was also partly supported by Theme-Based Research Scheme (T11706/18-N to ZC). Conflict of Interest: The authors declare no competing interests except that some authors are co-inventers of the presented HuNAbs in a patent application. Ethical Approval: This study was approved by the Institutional Review Board of University of Hong Kong/Hospital Authority Hong Kong West Cluster, Hong Kong East Cluster Research Ethics Committee, and Kowloon West Cluster Research Ethics Committee (UW 13-265, HKECREC-2018-068, KW/EX-20-038[144-26]).