Open AccessEarly treatment with a combination of two potent neutralizing antibodies improves clinical outcomes and reduces virus replication and lung inflammation in SARS-CoV-2 infected macaques
Author(s) -
Koen K. A. Van Rompay,
Katherine J. Olstad,
Rebecca L. Sammak,
Joseph Dutra,
Jennifer Watanabe,
Jodie Usachenko,
Ramya Immareddy,
Anil Verma,
Yashavanth Shaan Lakshmanappa,
Brian Schmidt,
Jamin W. Roh,
Sonny R. Elizaldi,
Ashley Allen,
Frauke Muecksch,
Julio C. C. Lorenzi,
Sarah H. Lockwood,
Rachel E. Pollard,
JoAnn Yee,
Peter B. Nham,
Amir Ardeshir,
Jesse D. Deere,
Jean L. Patterson,
Que Dang,
Théodora Hatziioannou,
Paul D. Bieniasz,
Smita S. Iyer,
Dennis J. Hartigan-O’Connor,
Michel C. Nussenzweig,
J. Rachel Reader
Publication year - 2021
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1009688
Subject(s) - monoclonal antibody , antibody , virology , immunology , medicine , neutralizing antibody , viral replication , monoclonal , pneumonia , macaque , virus , rhesus macaque , lung , biology , paleontology
There is an urgent need for effective therapeutic interventions against SARS-CoV-2, including new variants that continue to arise. Neutralizing monoclonal antibodies have shown promise in clinical studies. We investigated the therapeutic efficacy of a combination of two potent monoclonal antibodies, C135-LS and C144-LS that carry half-life extension mutations, in the rhesus macaque model of COVID-19. Twelve young adult macaques (three groups of four animals) were inoculated intranasally and intra-tracheally with a high dose of SARS-CoV-2 and 24 hours later, treated intravenously with a high (40 mg/kg) or low (12 mg/kg) dose of the C135-LS and C144-LS antibody combination, or a control monoclonal antibody. Animals were monitored for 7 days. Compared to the control animals, animals treated with either dose of the anti-SARS-CoV-2 antibodies showed similarly improved clinical scores, lower levels of virus replication in upper and lower respiratory tract, and significantly reduced interstitial pneumonia, as measured by comprehensive lung histology. In conclusion, this study provides proof-of-concept in support of further clinical development of these monoclonal antibodies against COVID-19 during early infection.