Nature Communications (Nov 2023)
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. Van Rompay,
- Phillip Lovalenti,
- Vu Truong,
- Donald N. Forthal,
- Nancy L. Haigwood
Affiliations
- Daniel N. Streblow
- Vaccine & Gene Therapy Institute, Oregon Health & Science University
- Alec J. Hirsch
- Vaccine & Gene Therapy Institute, Oregon Health & Science University
- Jeffrey J. Stanton
- Oregon National Primate Research Center, Oregon Health & Science University
- Anne D. Lewis
- Oregon National Primate Research Center, Oregon Health & Science University
- Lois Colgin
- Oregon National Primate Research Center, Oregon Health & Science University
- Ann J. Hessell
- Oregon National Primate Research Center, Oregon Health & Science University
- Craig N. Kreklywich
- Vaccine & Gene Therapy Institute, Oregon Health & Science University
- Jessica L. Smith
- Vaccine & Gene Therapy Institute, Oregon Health & Science University
- William F. Sutton
- Oregon National Primate Research Center, Oregon Health & Science University
- David Chauvin
- Aridis Pharmaceuticals
- Jennifer Woo
- Aridis Pharmaceuticals
- Benjamin N. Bimber
- Oregon National Primate Research Center, Oregon Health & Science University
- Cierra N. LeBlanc
- Department of Molecular and Medical Genetics, Oregon Health & Science University
- Sonia N. Acharya
- Department of Molecular and Medical Genetics, Oregon Health & Science University
- Brian J. O’Roak
- Department of Molecular and Medical Genetics, Oregon Health & Science University
- Harjinder Sardar
- Environmental Health & Safety, Oregon Health & Science University
- Mohammad M. Sajadi
- Baltimore VA Medical Center, VA Maryland Health Care System
- Zahra R. Tehrani
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland
- Mark R. Walter
- Department of Microbiology, University of Alabama at Birmingham
- Luis Martinez-Sobrido
- Texas Biomedical Research Institute
- James J. Kobie
- Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham
- Rachel J. Reader
- California National Primate Research Center, University of California
- Katherine J. Olstad
- California National Primate Research Center, University of California
- Theodore R. Hobbs
- Oregon National Primate Research Center, Oregon Health & Science University
- Erica Ollmann Saphire
- Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology
- Sharon L. Schendel
- Center for Infectious Disease and Vaccine Research, 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. Van Rompay
- California National Primate Research Center, University of California
- Phillip Lovalenti
- Aridis Pharmaceuticals
- Vu Truong
- Aridis Pharmaceuticals
- Donald N. Forthal
- University of California, Irvine, School of Medicine
- Nancy L. Haigwood
- Oregon National Primate Research Center, Oregon Health & Science University
- DOI
- https://doi.org/10.1038/s41467-023-42440-x
- Journal volume & issue
-
Vol. 14,
no. 1
pp. 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.
