Early treatment with a combination of two potent neutralizing antibodies improves clinical outcomes and reduces virus replication and lung inflammation in SARSCoV- 2 infected macaques

K. K.A. Rompay, Katherine J. Olstad, Rebecca L. Sammak, Joseph Dutra, Jennifer K. Watanabe, Jodie L. Usachenko, Ramya Immareddy, Anil Verma, Yashavanth Shaan Lakshmanappa, Brian A. Schmidt, Jamin W. Roh, Sonny R. Elizaldi, A. Mark Allen, Frauke Muecksch, Julio C.C. Lorenzi, Sarah Lockwood, Rachel E. Pollard, Jo Ann L. Yee, Peter B. Nham, Amir ArdeshirJesse D. Deere, Jean Patterson, Que Dang, Theodora Hatziioannou, Paul D. Bieniasz, Smita S. Iyer, Dennis J. Hartigan-O'connor, Michel C. Nussenzweig, J. Rachel Reader

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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.

Original languageEnglish (US)
Article numbere1009688
JournalPLoS pathogens
Volume17
Issue number7
DOIs
StatePublished - Jul 2021

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

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