1. Monoclonal antibodies protect aged rhesus macaques from SARS-CoV-2-induced immune activation and neuroinflammation.
- Author
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Verma, Anil, Hawes, Chase E, Lakshmanappa, Yashavanth Shaan, Roh, Jamin W, Schmidt, Brian A, Dutra, Joseph, Louie, William, Liu, Hongwei, Ma, Zhong-Min, Watanabe, Jennifer K, Usachenko, Jodie L, Immareddy, Ramya, Sammak, Rebecca L, Pollard, Rachel, Reader, J Rachel, Olstad, Katherine J, Coffey, Lark L, Kozlowski, Pamela A, Hartigan-O'Connor, Dennis J, Nussenzweig, Michel, Van Rompay, Koen KA, Morrison, John H, and Iyer, Smita S
- Subjects
NeuroCOVID ,inflammation ,SARS-CoV-2 ,cerebrospinal fluid ,effector CD4 T cells ,interstitial pneumonia ,lymph node ,neuroinflammation ,pathogenesis ,rhesus macaques ,Aging ,Animals ,Antibodies ,Monoclonal ,COVID-19 ,Diabetes Complications ,Diabetes Mellitus ,Experimental ,Female ,Humans ,Lymphocyte Activation ,Macaca mulatta ,Male ,Neuritis ,Pre-Exposure Prophylaxis ,T-Lymphocytes ,Virus Replication ,Prevention ,Biodefense ,Infectious Diseases ,Pneumonia ,Immunization ,Biotechnology ,Pneumonia & Influenza ,Emerging Infectious Diseases ,Lung ,Diabetes ,Vaccine Related ,receptor binding domain ,aged ,type 2 diabetic ,neutrophils ,mucosal-associated invariant T cells ,Biochemistry and Cell Biology ,Medical Physiology - 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.
- Published
- 2021