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

Daniel N. Streblow, Alec J. Hirsch, Jeffrey J. Stanton, Anne D. Lewis, Lois Colgin, Ann J. Hessell, Craig N. Kreklywich, Jessica L. Smith, William F. Sutton, David Chauvin, Jennifer Woo, Benjamin N. Bimber, Cierra N. LeBlanc, Sonia N. Acharya, Brian J. O’Roak, Harjinder Sardar, Mohammad M. Sajadi, Zahra R. Tehrani, Mark R. Walter, Luis Martinez-Sobrido, James J. Kobie, Rachel J. Reader, Katherine J. Olstad, Theodore R. Hobbs, Erica Ollmann Saphire, Sharon L. Schendel, Robert H. Carnahan, Jonas Knoch, Luis M. Branco, James E. Crowe, Koen K. A. Rompay, Phillip Lovalenti, Truong (), Donald N. Forthal () and Nancy L. Haigwood ()
Additional contact information
Daniel N. Streblow: Oregon Health & Science University
Alec J. Hirsch: Oregon Health & Science University
Jeffrey J. Stanton: Oregon Health & Science University
Anne D. Lewis: Oregon Health & Science University
Lois Colgin: Oregon Health & Science University
Ann J. Hessell: Oregon Health & Science University
Craig N. Kreklywich: Oregon Health & Science University
Jessica L. Smith: Oregon Health & Science University
William F. Sutton: Oregon Health & Science University
David Chauvin: Aridis Pharmaceuticals
Jennifer Woo: Aridis Pharmaceuticals
Benjamin N. Bimber: Oregon Health & Science University
Cierra N. LeBlanc: Oregon Health & Science University
Sonia N. Acharya: Oregon Health & Science University
Brian J. O’Roak: Oregon Health & Science University
Harjinder Sardar: Oregon Health & Science University
Mohammad M. Sajadi: VA Maryland Health Care System
Zahra R. Tehrani: University of Maryland
Mark R. Walter: University of Alabama at Birmingham
Luis Martinez-Sobrido: Texas Biomedical Research Institute
James J. Kobie: University of Alabama at Birmingham
Rachel J. Reader: University of California
Katherine J. Olstad: University of California
Theodore R. Hobbs: Oregon Health & Science University
Erica Ollmann Saphire: La Jolla Institute for Immunology
Sharon L. Schendel: La Jolla Institute for Immunology
Robert H. Carnahan: Vanderbilt University Medical Center
Jonas Knoch: PARI Pharma GmbH
Luis M. Branco: Zalgen Labs, LLC
James E. Crowe: Vanderbilt University Medical Center
Koen K. A. Rompay: University of California
Phillip Lovalenti: Aridis Pharmaceuticals
Truong: Aridis Pharmaceuticals
Donald N. Forthal: University of California, Irvine, School of Medicine
Nancy L. Haigwood: Oregon Health & Science University

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: Abstract 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.

Date: 2023
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DOI: 10.1038/s41467-023-42440-x

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