Development of an In Vivo Probe to Track SARS-CoV-2 Infection in Rhesus Macaques

Patrick J. Madden; Muhammad S. Arif; Mark E. Becker; Michael D. McRaven; Ann M. Carias; Ramon Lorenzo-Redondo; Sixia Xiao; Cecily C. Midkiff; Robert V. Blair; Elizabeth Lake Potter; Laura Martin-Sancho; Alan Dodson; Elena Martinelli; John Paul M. Todd; Francois J. Villinger; Sumit K. Chanda; Pyone Pyone Aye; Chad J. Roy; Mario Roederer; Mark G. Lewis; Ronald S. Veazey; Thomas J. Hope

doi:10.3389/fimmu.2021.810047

Development of an In Vivo Probe to Track SARS-CoV-2 Infection in Rhesus Macaques

Patrick J. Madden, Muhammad S. Arif, Mark E. Becker, Michael D. McRaven, Ann M. Carias, Ramon Lorenzo-Redondo, Sixia Xiao, Cecily C. Midkiff, Robert V. Blair, Elizabeth Lake Potter, Laura Martin-Sancho, Alan Dodson, Elena Martinelli, John Paul M. Todd, Francois J. Villinger, Sumit K. Chanda, Pyone Pyone Aye, Chad J. Roy, Mario Roederer, Mark G. LewisRonald S. Veazey, Thomas J. Hope^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

Infection with the novel coronavirus, SARS-CoV-2, results in pneumonia and other respiratory symptoms as well as pathologies at diverse anatomical sites. An outstanding question is whether these diverse pathologies are due to replication of the virus in these anatomical compartments and how and when the virus reaches those sites. To answer these outstanding questions and study the spatiotemporal dynamics of SARS-CoV-2 infection a method for tracking viral spread in vivo is needed. We developed a novel, fluorescently labeled, antibody-based in vivo probe system using the anti-spike monoclonal antibody CR3022 and demonstrated that it could successfully identify sites of SARS-CoV-2 infection in a rhesus macaque model of COVID-19. Our results showed that the fluorescent signal from our antibody-based probe could differentiate whole lungs of macaques infected for 9 days from those infected for 2 or 3 days. Additionally, the probe signal corroborated the frequency and density of infected cells in individual tissue blocks from infected macaques. These results provide proof of concept for the use of in vivo antibody-based probes to study SARS-CoV-2 infection dynamics in rhesus macaques.

Original language	English (US)
Article number	810047
Journal	Frontiers in immunology
Volume	12
DOIs	https://doi.org/10.3389/fimmu.2021.810047
State	Published - Dec 24 2021

Funding

This work was supported by National Institutes of Health grant R37 AI 094595-09S1 and in part by HHSN272201700033I (CR). This work was also supported in part by NIH grant OD011104. AC was supported in part by K01 OD026571-01. We thank Dr. Thomas Gallagher (Stritch School of Medicine, Loyola University Chicago, Chicago, IL) for the SARS-CoV-2 spike plasmid.

Keywords

COVID-19
SARS-CoV-2
antibodies
antibody probes
nonhuman primates
rhesus macaque

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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10.3389/fimmu.2021.810047

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Madden, P. J., Arif, M. S., Becker, M. E., McRaven, M. D., Carias, A. M., Lorenzo-Redondo, R., Xiao, S., Midkiff, C. C., Blair, R. V., Potter, E. L., Martin-Sancho, L., Dodson, A., Martinelli, E., Todd, J. P. M., Villinger, F. J., Chanda, S. K., Aye, P. P., Roy, C. J., Roederer, M., ... Hope, T. J. (2021). Development of an In Vivo Probe to Track SARS-CoV-2 Infection in Rhesus Macaques. Frontiers in immunology, 12, Article 810047. https://doi.org/10.3389/fimmu.2021.810047

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title = "Development of an In Vivo Probe to Track SARS-CoV-2 Infection in Rhesus Macaques",

abstract = "Infection with the novel coronavirus, SARS-CoV-2, results in pneumonia and other respiratory symptoms as well as pathologies at diverse anatomical sites. An outstanding question is whether these diverse pathologies are due to replication of the virus in these anatomical compartments and how and when the virus reaches those sites. To answer these outstanding questions and study the spatiotemporal dynamics of SARS-CoV-2 infection a method for tracking viral spread in vivo is needed. We developed a novel, fluorescently labeled, antibody-based in vivo probe system using the anti-spike monoclonal antibody CR3022 and demonstrated that it could successfully identify sites of SARS-CoV-2 infection in a rhesus macaque model of COVID-19. Our results showed that the fluorescent signal from our antibody-based probe could differentiate whole lungs of macaques infected for 9 days from those infected for 2 or 3 days. Additionally, the probe signal corroborated the frequency and density of infected cells in individual tissue blocks from infected macaques. These results provide proof of concept for the use of in vivo antibody-based probes to study SARS-CoV-2 infection dynamics in rhesus macaques.",

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author = "Madden, {Patrick J.} and Arif, {Muhammad S.} and Becker, {Mark E.} and McRaven, {Michael D.} and Carias, {Ann M.} and Ramon Lorenzo-Redondo and Sixia Xiao and Midkiff, {Cecily C.} and Blair, {Robert V.} and Potter, {Elizabeth Lake} and Laura Martin-Sancho and Alan Dodson and Elena Martinelli and Todd, {John Paul M.} and Villinger, {Francois J.} and Chanda, {Sumit K.} and Aye, {Pyone Pyone} and Roy, {Chad J.} and Mario Roederer and Lewis, {Mark G.} and Veazey, {Ronald S.} and Hope, {Thomas J.}",

note = "Publisher Copyright: Copyright {\textcopyright} 2021 Madden, Arif, Becker, McRaven, Carias, Lorenzo-Redondo, Xiao, Midkiff, Blair, Potter, Martin-Sancho, Dodson, Martinelli, Todd, Villinger, Chanda, Aye, Roy, Roederer, Lewis, Veazey and Hope.",

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Madden, PJ, Arif, MS, Becker, ME, McRaven, MD, Carias, AM , Lorenzo-Redondo, R, Xiao, S, Midkiff, CC, Blair, RV, Potter, EL, Martin-Sancho, L, Dodson, A, Martinelli, E, Todd, JPM, Villinger, FJ, Chanda, SK, Aye, PP, Roy, CJ, Roederer, M, Lewis, MG, Veazey, RS & Hope, TJ 2021, 'Development of an In Vivo Probe to Track SARS-CoV-2 Infection in Rhesus Macaques', Frontiers in immunology, vol. 12, 810047. https://doi.org/10.3389/fimmu.2021.810047

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AU - Madden, Patrick J.

AU - Arif, Muhammad S.

AU - Becker, Mark E.

AU - McRaven, Michael D.

AU - Carias, Ann M.

AU - Lorenzo-Redondo, Ramon

AU - Xiao, Sixia

AU - Midkiff, Cecily C.

AU - Blair, Robert V.

AU - Potter, Elizabeth Lake

AU - Martin-Sancho, Laura

AU - Dodson, Alan

AU - Martinelli, Elena

AU - Todd, John Paul M.

AU - Villinger, Francois J.

AU - Chanda, Sumit K.

AU - Aye, Pyone Pyone

AU - Roy, Chad J.

AU - Roederer, Mario

AU - Lewis, Mark G.

AU - Veazey, Ronald S.

AU - Hope, Thomas J.

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N2 - Infection with the novel coronavirus, SARS-CoV-2, results in pneumonia and other respiratory symptoms as well as pathologies at diverse anatomical sites. An outstanding question is whether these diverse pathologies are due to replication of the virus in these anatomical compartments and how and when the virus reaches those sites. To answer these outstanding questions and study the spatiotemporal dynamics of SARS-CoV-2 infection a method for tracking viral spread in vivo is needed. We developed a novel, fluorescently labeled, antibody-based in vivo probe system using the anti-spike monoclonal antibody CR3022 and demonstrated that it could successfully identify sites of SARS-CoV-2 infection in a rhesus macaque model of COVID-19. Our results showed that the fluorescent signal from our antibody-based probe could differentiate whole lungs of macaques infected for 9 days from those infected for 2 or 3 days. Additionally, the probe signal corroborated the frequency and density of infected cells in individual tissue blocks from infected macaques. These results provide proof of concept for the use of in vivo antibody-based probes to study SARS-CoV-2 infection dynamics in rhesus macaques.

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Development of an In Vivo Probe to Track SARS-CoV-2 Infection in Rhesus Macaques

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