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 E Pollard, J. Rachel Reader, Katherine J. Olstad, Lark L. Coffey, Pamela A. Kozlowski, Dennis J. Hartigan-O'Connor, Michel NussenzweigKoen K.A. Van Rompay, John Morrison, Smita Iyer

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article number109942
JournalCell Reports
Volume37
Issue number5
DOIs
StatePublished - Nov 2 2021

Keywords

  • cerebrospinal fluid
  • effector CD4 T cells
  • interstitial pneumonia
  • lymph node
  • NeuroCOVID, inflammation
  • neuroinflammation
  • pathogenesis
  • rhesus macaques
  • SARS-CoV-2

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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