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Nat Commun
. 2023 Nov 3;14(1):7062.
doi: 10.1038/s41467-023-42440-x. Aerosol delivery of SARS-CoV-2 human monoclonal antibodies in macaques limits viral replication and lung pathology
Daniel N Streblow 1 , Alec J Hirsch 1 , Jeffrey J Stanton 2 , Anne D Lewis 2 , Lois Colgin 2 , Ann J Hessell 2 , Craig N Kreklywich 1 , Jessica L Smith 1 , William F Sutton 2 , David Chauvin 3 , Jennifer Woo 3 , Benjamin N Bimber 2 , Cierra N LeBlanc 4 , Sonia N Acharya 4 , Brian J O'Roak 4 , Harjinder Sardar 5 , Mohammad M Sajadi 6 , Zahra R Tehrani 7 , Mark R Walter 8 , Luis Martinez-Sobrido 9 , James J Kobie 10 , Rachel J Reader 11 , Katherine J Olstad 11 , Theodore R Hobbs 2 , Erica Ollmann Saphire 12 , Sharon L Schendel 12 , Robert H Carnahan 13 , Jonas Knoch 14 , Luis M Branco 15 , James E Crowe Jr 13 , Koen K A Van Rompay 11 , Phillip Lovalenti 3 , Vu Truong 16 , Donald N Forthal 17 , Nancy L Haigwood 18
Affiliations
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.
. 2023 Nov 3;14(1):7062.
doi: 10.1038/s41467-023-42440-x. Aerosol delivery of SARS-CoV-2 human monoclonal antibodies in macaques limits viral replication and lung pathology
Daniel N Streblow 1 , Alec J Hirsch 1 , Jeffrey J Stanton 2 , Anne D Lewis 2 , Lois Colgin 2 , Ann J Hessell 2 , Craig N Kreklywich 1 , Jessica L Smith 1 , William F Sutton 2 , David Chauvin 3 , Jennifer Woo 3 , Benjamin N Bimber 2 , Cierra N LeBlanc 4 , Sonia N Acharya 4 , Brian J O'Roak 4 , Harjinder Sardar 5 , Mohammad M Sajadi 6 , Zahra R Tehrani 7 , Mark R Walter 8 , Luis Martinez-Sobrido 9 , James J Kobie 10 , Rachel J Reader 11 , Katherine J Olstad 11 , Theodore R Hobbs 2 , Erica Ollmann Saphire 12 , Sharon L Schendel 12 , Robert H Carnahan 13 , Jonas Knoch 14 , Luis M Branco 15 , James E Crowe Jr 13 , Koen K A Van Rompay 11 , Phillip Lovalenti 3 , Vu Truong 16 , Donald N Forthal 17 , Nancy L Haigwood 18
Affiliations
- PMID: 37923717
- PMCID: PMC10624670
- DOI: 10.1038/s41467-023-42440-x
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.