Journal Article

Aerosol delivery of SARS-CoV-2 human monoclonal antibodies in macaques limits viral replication and lung pathology

Hessell, Ann J., Martinez-Sobrido, Luis, Carnahan, Robert H., Walter, Mark R., LeBlanc, Cierra N., Smith, Jessica L., Saphire, Erica Ollmann, Van Rompay, Koen K. A., Hobbs, Theodore R., Vu Truong, Streblow, Daniel N., Acharya, Sonia N., Forthal, Donald N., Sardar, Harjinder, Crowe, James E., Woo, Jennifer, Bimber, Benjamin N., Sajadi, Mohammad M., Tehrani, Zahra R., Reader, Rachel J., Knoch, Jonas, Colgin, Lois, Lewis, Anne D., Hirsch, Alec J., Schendel, Sharon L., Haigwood, Nancy L., Olstad, Katherine J., Branco, Luis M., Kreklywich, Craig N., O’Roak, Brian J., Stanton, Jeffrey J., Lovalenti, Phillip, Kobie, James J., Sutton, William F., Chauvin, David

2023

Overview

Passively administered monoclonal antibodies (mAbs) given before or after viral infection can prevent or blunt disease. Here, we examine the efficacy of aerosol mAb delivery to prevent infection and disease in rhesus macaques inoculated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant via intranasal and intratracheal routes. SARS-CoV-2 human mAbs or a human mAb directed to respiratory syncytial virus (RSV) are nebulized and delivered using positive airflow via facemask to sedated macaques pre- and post-infection. Nebulized human mAbs are detectable in nasal, oropharyngeal, and bronchoalveolar lavage (BAL) samples. SARS-CoV-2 mAb treatment significantly reduces levels of SARS-CoV-2 viral RNA and infectious virus in the upper and lower respiratory tracts relative to controls. Reductions in lung and BAL virus levels correspond to reduced BAL inflammatory cytokines and lung pathology. Aerosolized antibody therapy for SARS-CoV-2 could be effective for reducing viral burden and limiting disease severity. Here the authors deliver aerosolized human monoclonal antibodies to SARS-CoV-2-infected rhesus macaques and show that the treatment significantly reduces viral RNA and infectious virus in the respiratory tracts, limits lung pathology, and decreases inflammatory cytokines.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13 / 13/1 / 13/106 / 13/21 / 45/23 / 631/250/251 / 631/326/596/4130 / 692/308/2778 / 82/1 / Aerosols / Air flow / Animals / Antibodies, Monoclonal / Antibodies, Viral / Bronchus / Coronaviruses / COVID-19 / COVID-19 - pathology / Cytokines / Health services / Humanities and Social Sciences / Humans / Immunotherapy / Infections / Inflammation / Lavage / Lung - pathology / Lungs / Macaca mulatta / Monoclonal antibodies / multidisciplinary / Pathology / Respiratory Aerosols and Droplets / Respiratory diseases / Respiratory syncytial virus / Respiratory tract / RNA viruses / SARS-CoV-2 / Science / Science (multidisciplinary) / Severe acute respiratory syndrome coronavirus 2 / Trachea / Viral diseases / Viral infections / Virus Replication / Viruses