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; Truong Vu Truong; Donald N. Forthal; Nancy L. Haigwood

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, 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-SobridoJames 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, Truong Vu Truong, Donald N. Forthal, Nancy L. Haigwood

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Article number	7062
Journal	Nature communications
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/s41467-023-42440-x
State	Published - Dec 2023

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

Access to Document

10.1038/s41467-023-42440-x

Cite this

Streblow, D. N., Hirsch, A. J., Stanton, J. J., Lewis, A. D., Colgin, L., Hessell, A. J., Kreklywich, C. N., Smith, J. L., Sutton, W. F., Chauvin, D., Woo, J., Bimber, B. N., LeBlanc, C. N., Acharya, S. N., O’Roak, B. J., Sardar, H., Sajadi, M. M., Tehrani, Z. R., Walter, M. R., ... Haigwood, N. L. (2023). Aerosol delivery of SARS-CoV-2 human monoclonal antibodies in macaques limits viral replication and lung pathology. Nature communications, 14(1), Article 7062. https://doi.org/10.1038/s41467-023-42440-x

Streblow, DN , Hirsch, AJ , Stanton, JJ , Lewis, AD , Colgin, L , Hessell, AJ, Kreklywich, CN, Smith, JL, Sutton, WF, Chauvin, D, Woo, J, Bimber, BN, LeBlanc, CN, Acharya, SN, O’Roak, BJ, Sardar, H, Sajadi, MM, Tehrani, ZR, Walter, MR, Martinez-Sobrido, L, Kobie, JJ, Reader, RJ, Olstad, KJ, Hobbs, TR, Saphire, EO, Schendel, SL, Carnahan, RH, Knoch, J, Branco, LM, Crowe, JE, Van Rompay, KKA, Lovalenti, P, Vu Truong, T, Forthal, DN & Haigwood, NL 2023, 'Aerosol delivery of SARS-CoV-2 human monoclonal antibodies in macaques limits viral replication and lung pathology', Nature communications, vol. 14, no. 1, 7062. https://doi.org/10.1038/s41467-023-42440-x

@article{dbcfdf66dfea4a2bb96f94fdd487d358,

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

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.",

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

note = "Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

month = dec,

doi = "10.1038/s41467-023-42440-x",

language = "English (US)",

volume = "14",

journal = "Nature communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

}

TY - JOUR

T1 - Aerosol delivery of SARS-CoV-2 human monoclonal antibodies in macaques limits viral replication and lung pathology

AU - Streblow, Daniel N.

AU - Hirsch, Alec J.

AU - Stanton, Jeffrey J.

AU - Lewis, Anne D.

AU - Colgin, Lois

AU - Hessell, Ann J.

AU - Kreklywich, Craig N.

AU - Smith, Jessica L.

AU - Sutton, William F.

AU - Chauvin, David

AU - Woo, Jennifer

AU - Bimber, Benjamin N.

AU - LeBlanc, Cierra N.

AU - Acharya, Sonia N.

AU - O’Roak, Brian J.

AU - Sardar, Harjinder

AU - Sajadi, Mohammad M.

AU - Tehrani, Zahra R.

AU - Walter, Mark R.

AU - Martinez-Sobrido, Luis

AU - Kobie, James J.

AU - Reader, Rachel J.

AU - Olstad, Katherine J.

AU - Hobbs, Theodore R.

AU - Saphire, Erica Ollmann

AU - Schendel, Sharon L.

AU - Carnahan, Robert H.

AU - Knoch, Jonas

AU - Branco, Luis M.

AU - Crowe, James E.

AU - Van Rompay, Koen K.A.

AU - Lovalenti, Phillip

AU - Vu Truong, Truong

AU - Forthal, Donald N.

AU - Haigwood, Nancy L.

PY - 2023/12

Y1 - 2023/12

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85175690759&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85175690759&partnerID=8YFLogxK

U2 - 10.1038/s41467-023-42440-x

DO - 10.1038/s41467-023-42440-x

M3 - Article

C2 - 37923717

AN - SCOPUS:85175690759

SN - 2041-1723

VL - 14

JO - Nature communications

JF - Nature communications

IS - 1

M1 - 7062

ER -

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

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this