Aerosol delivery of SARS-CoV-2 human monoclonal antibodies in macaques limits viral replication and lung pathology
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Published:2023-11-03
Issue:1
Volume:14
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Streblow Daniel N., Hirsch Alec J.ORCID, Stanton Jeffrey J., Lewis Anne D.ORCID, Colgin Lois, Hessell Ann J., Kreklywich Craig N., Smith Jessica L., Sutton William F., Chauvin David, Woo JenniferORCID, Bimber Benjamin N.ORCID, LeBlanc Cierra N., Acharya Sonia N., O’Roak Brian J.ORCID, Sardar Harjinder, Sajadi Mohammad M., Tehrani Zahra R., Walter Mark R.ORCID, Martinez-Sobrido LuisORCID, Kobie James J.ORCID, Reader Rachel J.ORCID, Olstad Katherine J., Hobbs Theodore R.ORCID, Saphire Erica OllmannORCID, Schendel Sharon L.ORCID, Carnahan Robert H., Knoch Jonas, Branco Luis M., Crowe James E., Van Rompay Koen K. A.ORCID, Lovalenti Phillip, Vu Truong , Forthal Donald N., Haigwood Nancy L.ORCID
Abstract
AbstractPassively 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.
Funder
U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases Bill and Melinda Gates Foundation Division of Intramural Research, National Institute of Allergy and Infectious Diseases Oregon Health & Science University Foundation funding to support SARS-CoV-2 sequencing
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
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