tetano
Editor, Senior Moderator
Cell Rep
. 2021 Oct 19;109942.
doi: 10.1016/j.celrep.2021.109942. Online ahead of print.
Monoclonal antibodies protect aged rhesus macaques from SARS-CoV-2-induced immune activation and neuroinflammation
Anil Verma[SUP] 1 [/SUP], Chase E Hawes[SUP] 2 [/SUP], Yashavanth Shaan Lakshmanappa[SUP] 1 [/SUP], Jamin W Roh[SUP] 2 [/SUP], Brian A Schmidt[SUP] 1 [/SUP], Joseph Dutra[SUP] 3 [/SUP], William Louie[SUP] 4 [/SUP], Hongwei Liu[SUP] 4 [/SUP], Zhong-Min Ma[SUP] 3 [/SUP], Jennifer K Watanabe[SUP] 3 [/SUP], Jodie L Usachenko[SUP] 3 [/SUP], Ramya Immareddy[SUP] 3 [/SUP], Rebecca L Sammak[SUP] 3 [/SUP], Rachel Pollard[SUP] 3 [/SUP], J Rachel Reader[SUP] 5 [/SUP], Katherine J Olstad[SUP] 5 [/SUP], Lark L Coffey[SUP] 4 [/SUP], Pamela A Kozlowski[SUP] 6 [/SUP], Dennis J Hartigan-O'Connor[SUP] 7 [/SUP], Michel Nussenzweig[SUP] 8 [/SUP], Koen K A Van Rompay[SUP] 5 [/SUP], John H Morrison[SUP] 9 [/SUP], Smita S Iyer[SUP] 10 [/SUP]
Affiliations
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.
Keywords: NeuroCOVID, inflammation; SARS-CoV-2; cerebrospinal fluid; effector CD4 T cells; interstitial pneumonia; lymph node; neuroinflammation; pathogenesis; rhesus macaques.
. 2021 Oct 19;109942.
doi: 10.1016/j.celrep.2021.109942. Online ahead of print.
Monoclonal antibodies protect aged rhesus macaques from SARS-CoV-2-induced immune activation and neuroinflammation
Anil Verma[SUP] 1 [/SUP], Chase E Hawes[SUP] 2 [/SUP], Yashavanth Shaan Lakshmanappa[SUP] 1 [/SUP], Jamin W Roh[SUP] 2 [/SUP], Brian A Schmidt[SUP] 1 [/SUP], Joseph Dutra[SUP] 3 [/SUP], William Louie[SUP] 4 [/SUP], Hongwei Liu[SUP] 4 [/SUP], Zhong-Min Ma[SUP] 3 [/SUP], Jennifer K Watanabe[SUP] 3 [/SUP], Jodie L Usachenko[SUP] 3 [/SUP], Ramya Immareddy[SUP] 3 [/SUP], Rebecca L Sammak[SUP] 3 [/SUP], Rachel Pollard[SUP] 3 [/SUP], J Rachel Reader[SUP] 5 [/SUP], Katherine J Olstad[SUP] 5 [/SUP], Lark L Coffey[SUP] 4 [/SUP], Pamela A Kozlowski[SUP] 6 [/SUP], Dennis J Hartigan-O'Connor[SUP] 7 [/SUP], Michel Nussenzweig[SUP] 8 [/SUP], Koen K A Van Rompay[SUP] 5 [/SUP], John H Morrison[SUP] 9 [/SUP], Smita S Iyer[SUP] 10 [/SUP]
Affiliations
- PMID: 34706272
- DOI: 10.1016/j.celrep.2021.109942
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.
Keywords: NeuroCOVID, inflammation; SARS-CoV-2; cerebrospinal fluid; effector CD4 T cells; interstitial pneumonia; lymph node; neuroinflammation; pathogenesis; rhesus macaques.