Monoclonal antibodies protect aged rhesus macaques from SARS-CoV-2-induced immune activation and neuroinflammation

单克隆抗体可保护老年恒河猴免受SARS-CoV-2诱导的免疫激活和神经炎症的影响

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作者: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

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.

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