Anti-viral monoclonal antibody (mAb) treatments may provide immediate but short-term immunity from COVID-19 in high-risk populations such as aged and diabetic individuals, however, data on their efficacy in these populations is limited. We demonstrate that prophylactic mAb treatment prevented viral replication specifically in the upper respiratory tract in aged, type-2-diabetic rhesus macaques. While activation of innate inflammatory pathways was observed, mAb infusion dramatically curtailed SARS-CoV-2-mediated stimulation of interferon-induced chemokines and T cell activation, significantly reducing the development of interstitial pneumonia. Effector T cell differentiation was reduced in the draining mediastinal lymph nodes, resulting in significantly lower representation of activated cells in the spleen and blood. Consequently, mAb infusion significantly dampened the greater than three-fold increase in SARS-CoV-2-induced effector CD4 T cell influx into the cerebrospinal fluid. Our data indicate that neutralizing mAbs administered preventatively to high-risk populations may mitigate the adverse inflammatory consequences of SARS-CoV-2 exposure.
Funding Information: This study was supported by grants R21 AI143454-02S1 (SSI), FAST GRANT- George Mason 358 University (SSI), 3RF1AG061001-01S1 (SSI/JHM) and the CNPRC base grant P51OD011107
Declaration of Interests: The authors declare no competing interests.
Ethics Approval Statement: All study procedures were approved by the Institutional Animal Care and Use Committee at UC Davis.
Keywords: receptor binding domain, rhesus macaques, aged, type 2 diabetic, neuroinflammation, neutrophils, lymph node, mucosal-associated invariant T cells
Verma, Anil and Hawes, Chase E. and Shaan Lakshmanppa, Yashavanth and Schmidt, Brian A. and Roh, Jamin W. and Dutra, Joseph and Louie, William and Liu, Hongwei and Ma, Zhong-Min and Watanabe, Jennifer K. and Usachenko, Jodie L. and Immareddy, Ramya and Sammak, Rebecca L. and Pollard, Rachel and Reader, Rachel and Olstad, Katherine J. and Coffey, Lark L. and Kozlowski, Pamela A. and Hartigan-O'Connor, Dennis J. and Nussenzweig, Michel and Van Rompay, Koen K.A and Morrison, John H. and Iyer, Smita S., Monoclonal Antibodies Protect Aged Rhesus Macaques From SARS-CoV2 Induced Immune Activation. Available at SSRN: https://ssrn.com/abstract=3886997 or http://dx.doi.org/10.2139/ssrn.3886997
This version of the paper has not been formally peer reviewed.
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