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 (IC 50 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.
【저자키워드】 COVID-19, SARS-CoV-2, Lung injury, Receptor binding domain, phage display, upper respiratory tract, human neutralizing antibody, nasal turbinate, 【초록키워드】 neutralizing antibody, viral infection, Vaccine, coronavirus, vaccination, therapy, antibody, Infection, lung, nasal, Angiotensin converting enzyme-2, DNA, Reinfection, Transmissibility, Viral load, RBD, Neutralizing, hamster, upper respiratory tract, SARS-CoV-2 replication, intranasal, binding, Injury, Receptor binding, lung damage, acute respiratory syndrome, injection, live SARS-CoV-2, implication, robust, upper respiratory, tested, significantly, intranasally, characterized, treated, determine, suppresse, reduce, competing, inhibit SARS-CoV-2, 【제목키워드】 Treatment, neutralizing antibody, SARS-COV-2 infection,