Robust SARS-CoV-2 infection in nasal turbinates after treatment with systemic neutralizing antibodies.

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.

• Authors: Dongyan Zhou, Jasper Fuk-Woo Chan, Biao Zhou, Runhong Zhou, Shuang Li, Sisi Shan, Li Liu, Anna Jinxia Zhang, Serena J Chen, Chris Chung-Sing Chan, Haoran Xu, Vincent Kwok-Man Poon, Shuofeng Yuan, Cun Li, Kenn Ka-Heng Chik, Chris Chun-Yiu Chan, Jianli Cao, Chun-Yin Chan, Ka-Yi Kwan, Zhenglong Du, Thomas Tsz-Kan Lau, Qi Zhang, Jie Zhou, Kelvin Kai-Wang To, Linqi Zhang, David D Ho, Kwok-Yung Yuen, Zhiwei Chen
• Journal: Cell host & microbe (Cell Host Microbe) Vol. 29 Issue 4 Pg. 551-563.e5 (04 14 2021) ISSN: 1934-6069 [Electronic] United States
• PMID: 33657424 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Neutralizing
• Antibodies, Viral
• Angiotensin-Converting Enzyme 2

Topics

• Angiotensin-Converting Enzyme 2 (physiology)
• Animals
• Antibodies, Neutralizing (immunology, therapeutic use)
• Antibodies, Viral (immunology, therapeutic use)
• COVID-19 (immunology, therapy, virology)
• Cricetinae
• Female
• HEK293 Cells
• Humans
• Male
• Mesocricetus
• SARS-CoV-2 (immunology)
• Turbinates (virology)
• Viral Load