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Cell Host Microbe
. 2021 Feb 25;S1931-3128(21)00098-6.
doi: 10.1016/j.chom.2021.02.019. Online ahead of print.
Robust SARS-CoV-2 infection in nasal turbinates after treatment with systemic neutralizing antibodies
Dongyan Zhou 1 , Jasper Fuk-Woo Chan 2 , Biao Zhou 1 , Runhong Zhou 1 , Shuang Li 1 , Sisi Shan 3 , Li Liu 1 , Anna Jinxia Zhang 4 , Serena J Chen 5 , Chris Chung-Sing Chan 6 , Haoran Xu 1 , Vincent Kwok-Man Poon 6 , Shuofeng Yuan 2 , Cun Li 6 , Kenn Ka-Heng Chik 6 , Chris Chun-Yiu Chan 6 , Jianli Cao 6 , Chun-Yin Chan 1 , Ka-Yi Kwan 1 , Zhenglong Du 1 , Thomas Tsz-Kan Lau 1 , Qi Zhang 3 , Jie Zhou 4 , Kelvin Kai-Wang To 2 , Linqi Zhang 3 , David D Ho 7 , Kwok-Yung Yuen 8 , Zhiwei Chen 9
Affiliations
- PMID: 33657424
- PMCID: PMC7904446
- DOI: 10.1016/j.chom.2021.02.019
Abstract
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 μg/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.
Keywords: COVID-19; SARS-CoV-2; human neutralizing antibody; lung injury; nasal turbinate; phage display; receptor binding domain; upper respiratory tract.