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 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

doi:10.1016/j.celrep.2021.109942

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 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 H. Morrison, Smita S. Iyer

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12 Scopus citations

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 language	English
Article number	109942
Journal	Cell Reports
Volume	37
Issue number	5
DOIs	https://doi.org/10.1016/j.celrep.2021.109942
State	Published - 2 Nov 2021
Externally published	Yes

Keywords

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

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10.1016/j.celrep.2021.109942

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Verma, A., Hawes, C. E., Lakshmanappa, Y. S., Roh, J. W., Schmidt, B. A., Dutra, J., Louie, W., Liu, H., Ma, Z. M., Watanabe, J. K., Usachenko, J. L., Immareddy, R., Sammak, R. L., Pollard, R., Reader, J. R., Olstad, K. J., Coffey, L. L., Kozlowski, P. A., Hartigan-O'Connor, D. J., ... Iyer, S. S. (2021). Monoclonal antibodies protect aged rhesus macaques from SARS-CoV-2-induced immune activation and neuroinflammation. Cell Reports, 37(5), Article 109942. https://doi.org/10.1016/j.celrep.2021.109942

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

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",

author = "Anil Verma and Hawes, {Chase E.} and Lakshmanappa, {Yashavanth Shaan} and Roh, {Jamin W.} and Schmidt, {Brian A.} and Joseph Dutra and William Louie and Hongwei Liu and Ma, {Zhong Min} and Watanabe, {Jennifer K.} and Usachenko, {Jodie L.} and Ramya Immareddy and Sammak, {Rebecca L.} and Rachel Pollard and Reader, {J. Rachel} and Olstad, {Katherine J.} and Coffey, {Lark L.} and Kozlowski, {Pamela A.} and Hartigan-O'Connor, {Dennis J.} and Michel Nussenzweig and {Van Rompay}, {Koen K.A.} and Morrison, {John H.} and Iyer, {Smita S.}",

note = "Publisher Copyright: {\textcopyright} 2021",

year = "2021",

month = nov,

day = "2",

doi = "10.1016/j.celrep.2021.109942",

language = "English",

volume = "37",

journal = "Cell Reports",

issn = "2211-1247",

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Verma, A, Hawes, CE, Lakshmanappa, YS, Roh, JW, Schmidt, BA, Dutra, J, Louie, W, Liu, H, Ma, ZM, Watanabe, JK, Usachenko, JL, Immareddy, R, Sammak, RL, Pollard, R, Reader, JR, Olstad, KJ, Coffey, LL, Kozlowski, PA, Hartigan-O'Connor, DJ, Nussenzweig, M, Van Rompay, KKA, Morrison, JH & Iyer, SS 2021, 'Monoclonal antibodies protect aged rhesus macaques from SARS-CoV-2-induced immune activation and neuroinflammation', Cell Reports, vol. 37, no. 5, 109942. https://doi.org/10.1016/j.celrep.2021.109942

TY - JOUR

T1 - Monoclonal antibodies protect aged rhesus macaques from SARS-CoV-2-induced immune activation and neuroinflammation

AU - Verma, Anil

AU - Hawes, Chase E.

AU - Lakshmanappa, Yashavanth Shaan

AU - Roh, Jamin W.

AU - Schmidt, Brian A.

AU - Dutra, Joseph

AU - Louie, William

AU - Liu, Hongwei

AU - Ma, Zhong Min

AU - Watanabe, Jennifer K.

AU - Usachenko, Jodie L.

AU - Immareddy, Ramya

AU - Sammak, Rebecca L.

AU - Pollard, Rachel

AU - Reader, J. Rachel

AU - Olstad, Katherine J.

AU - Coffey, Lark L.

AU - Kozlowski, Pamela A.

AU - Hartigan-O'Connor, Dennis J.

AU - Nussenzweig, Michel

AU - Van Rompay, Koen K.A.

AU - Morrison, John H.

AU - Iyer, Smita S.

PY - 2021/11/2

Y1 - 2021/11/2

N2 - 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.

AB - 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.

KW - NeuroCOVID, inflammation

KW - SARS-CoV-2

KW - cerebrospinal fluid

KW - effector CD4 T cells

KW - interstitial pneumonia

KW - lymph node

KW - neuroinflammation

KW - pathogenesis

KW - rhesus macaques

UR - http://www.scopus.com/inward/record.url?scp=85118509660&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2021.109942

DO - 10.1016/j.celrep.2021.109942

M3 - Article

C2 - 34706272

AN - SCOPUS:85118509660

SN - 2211-1247

VL - 37

JO - Cell Reports

JF - Cell Reports

IS - 5

M1 - 109942

ER -

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

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Keywords

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