Cell Reports (Nov 2021)
Monoclonal antibodies protect aged rhesus macaques from SARS-CoV-2-induced immune activation and neuroinflammation
- Anil Verma,
- Chase E. Hawes,
- Yashavanth Shaan Lakshmanappa,
- Jamin W. Roh,
- Brian A. Schmidt,
- Joseph Dutra,
- William Louie,
- Hongwei Liu,
- Zhong-Min Ma,
- Jennifer K. Watanabe,
- Jodie L. Usachenko,
- Ramya Immareddy,
- Rebecca L. Sammak,
- Rachel Pollard,
- J. Rachel Reader,
- Katherine J. Olstad,
- Lark L. Coffey,
- Pamela A. Kozlowski,
- Dennis J. Hartigan-O’Connor,
- Michel Nussenzweig,
- Koen K.A. Van Rompay,
- John H. Morrison,
- Smita S. Iyer
Affiliations
- Anil Verma
- Center for Immunology and Infectious Diseases, University of California, Davis, Davis, CA 95616, USA
- Chase E. Hawes
- Center for Immunology and Infectious Diseases, University of California, Davis, Davis, CA 95616, USA; Graduate Group in Immunology, University of California, Davis, Davis, CA 95616, USA
- Yashavanth Shaan Lakshmanappa
- Center for Immunology and Infectious Diseases, University of California, Davis, Davis, CA 95616, USA
- Jamin W. Roh
- Center for Immunology and Infectious Diseases, University of California, Davis, Davis, CA 95616, USA; Graduate Group in Immunology, University of California, Davis, Davis, CA 95616, USA
- Brian A. Schmidt
- Center for Immunology and Infectious Diseases, University of California, Davis, Davis, CA 95616, USA
- Joseph Dutra
- California National Primate Research Center, University of California, Davis, Davis, CA 95616, USA
- William Louie
- Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, Davis, CA 95616, USA
- Hongwei Liu
- Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, Davis, CA 95616, USA
- Zhong-Min Ma
- California National Primate Research Center, University of California, Davis, Davis, CA 95616, USA
- Jennifer K. Watanabe
- California National Primate Research Center, University of California, Davis, Davis, CA 95616, USA
- Jodie L. Usachenko
- California National Primate Research Center, University of California, Davis, Davis, CA 95616, USA
- Ramya Immareddy
- California National Primate Research Center, University of California, Davis, Davis, CA 95616, USA
- Rebecca L. Sammak
- California National Primate Research Center, University of California, Davis, Davis, CA 95616, USA
- Rachel Pollard
- California National Primate Research Center, University of California, Davis, Davis, CA 95616, USA
- J. Rachel Reader
- California National Primate Research Center, University of California, Davis, Davis, CA 95616, USA; Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, Davis, CA 95616, USA
- Katherine J. Olstad
- California National Primate Research Center, University of California, Davis, Davis, CA 95616, USA; Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, Davis, CA 95616, USA
- Lark L. Coffey
- Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, Davis, CA 95616, USA
- Pamela A. Kozlowski
- Department of Microbiology, Immunology, and Parasitology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
- Dennis J. Hartigan-O’Connor
- California National Primate Research Center, University of California, Davis, Davis, CA 95616, USA; Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, CA 95616, USA
- Michel Nussenzweig
- Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
- Koen K.A. Van Rompay
- California National Primate Research Center, University of California, Davis, Davis, CA 95616, USA; Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, Davis, CA 95616, USA
- John H. Morrison
- California National Primate Research Center, University of California, Davis, Davis, CA 95616, USA; Department of Neurology, School of Medicine, University of California, Davis, Davis, CA 95616, USA
- Smita S. Iyer
- Center for Immunology and Infectious Diseases, University of California, Davis, Davis, CA 95616, USA; California National Primate Research Center, University of California, Davis, Davis, CA 95616, USA; Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, Davis, CA 95616, USA; Corresponding author
- Journal volume & issue
-
Vol. 37,
no. 5
p. 109942
Abstract
Summary: Anti-viral monoclonal antibody (mAb) treatments may provide immediate but short-term immunity from coronavirus disease 2019 (COVID-19) in high-risk populations, such as people with diabetes and the elderly; however, data on their efficacy in these populations are limited. We demonstrate that prophylactic mAb treatment blocks viral replication in both the upper and lower respiratory tracts in aged, type 2 diabetic rhesus macaques. mAb infusion dramatically curtails severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-mediated stimulation of interferon-induced chemokines and T cell activation, significantly reducing development of interstitial pneumonia. Furthermore, mAb infusion significantly dampens the greater than 3-fold increase in SARS-CoV-2-induced effector CD4 T cell influx into the cerebrospinal fluid. Our data show that neutralizing mAbs administered preventatively to high-risk populations may mitigate the adverse inflammatory consequences of SARS-CoV-2 exposure.
