TY - JOUR
T1 - Robust SARS-CoV-2 infection in nasal turbinates after treatment with systemic neutralizing antibodies
AU - Zhou, Dongyan
AU - Chan, Jasper Fuk Woo
AU - Zhou, Biao
AU - Zhou, Runhong
AU - Li, Shuang
AU - Shan, Sisi
AU - Liu, Li
AU - Zhang, Anna Jinxia
AU - Chen, Serena J.
AU - Chan, Chris Chung Sing
AU - Xu, Haoran
AU - Poon, Vincent Kwok Man
AU - Yuan, Shuofeng
AU - Li, Cun
AU - Chik, Kenn Ka Heng
AU - Chan, Chris Chun Yiu
AU - Cao, Jianli
AU - Chan, Chun Yin
AU - Kwan, Ka Yi
AU - Du, Zhenglong
AU - Lau, Thomas Tsz Kan
AU - Zhang, Qi
AU - Zhou, Jie
AU - To, Kelvin Kai Wang
AU - Zhang, Linqi
AU - Ho, David D.
AU - Yuen, Kwok Yung
AU - Chen, Zhiwei
N1 - Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2021/4/14
Y1 - 2021/4/14
N2 - 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.
AB - 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.
KW - COVID-19
KW - SARS-CoV-2
KW - human neutralizing antibody
KW - lung injury
KW - nasal turbinate
KW - phage display
KW - receptor binding domain
KW - upper respiratory tract
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UR - http://www.scopus.com/inward/citedby.url?scp=85101883548&partnerID=8YFLogxK
U2 - 10.1016/j.chom.2021.02.019
DO - 10.1016/j.chom.2021.02.019
M3 - Article
C2 - 33657424
AN - SCOPUS:85101883548
SN - 1931-3128
VL - 29
SP - 551-563.e5
JO - Cell Host and Microbe
JF - Cell Host and Microbe
IS - 4
ER -