1. Early 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
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Van Rompay KKA, Olstad KJ, Sammak RL, Dutra J, Watanabe JK, Usachenko JL, Immareddy R, Verma A, Shaan Lakshmanappa Y, Schmidt BA, Roh JW, Elizaldi SR, Allen AM, Muecksch F, Lorenzi JCC, Lockwood S, Pollard RE, Yee JL, Nham PB, Ardeshir A, Deere JD, Patterson J, Dang Q, Hatziioannou T, Bieniasz PD, Iyer SS, Hartigan-O'Connor DJ, Nussenzweig MC, and Reader JR
- Subjects
- Animals, Antibodies, Monoclonal blood, Antibodies, Monoclonal immunology, Antibodies, Monoclonal therapeutic use, Antibodies, Neutralizing blood, Antibodies, Neutralizing immunology, Antibodies, Viral blood, Antibodies, Viral immunology, COVID-19 pathology, COVID-19 virology, Disease Models, Animal, Female, Lung diagnostic imaging, Macaca mulatta, Male, Multivariate Analysis, Radiography, Respiratory System virology, SARS-CoV-2 physiology, Time Factors, Treatment Outcome, Antibodies, Neutralizing therapeutic use, Antibodies, Viral therapeutic use, COVID-19 therapy, Lung pathology, SARS-CoV-2 immunology, Virus Replication immunology
- Abstract
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., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Rockefeller University has submitted a patent application for C135-LS and C144-LS on which MCN is an inventor. MCN and PDB are HHMI investigators.
- Published
- 2021
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