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

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...

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Published inFrontiers in immunology Vol. 12; p. 810047
Main Authors Madden, Patrick J, Arif, Muhammad S, Becker, Mark E, McRaven, Michael D, Carias, Ann M, Lorenzo-Redondo, Ramon, Xiao, Sixia, Midkiff, Cecily C, Blair, Robert V, Potter, Elizabeth Lake, Martin-Sancho, Laura, Dodson, Alan, Martinelli, Elena, Todd, John-Paul M, Villinger, Francois J, Chanda, Sumit K, Aye, Pyone Pyone, Roy, Chad J, Roederer, Mario, Lewis, Mark G, Veazey, Ronald S, Hope, Thomas J
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 24.12.2021
Subjects
Animals
antibodies
Antibodies, Monoclonal - immunology
Antibodies, Neutralizing - immunology
Antibodies, Viral - immunology
antibody probes
Cell Line
COVID-19
COVID-19 - pathology
Disease Models, Animal
Fluorescent Antibody Technique - methods
Humans
Immunology
Lung - pathology
Lung - virology
Macaca mulatta
nonhuman primates
Proof of Concept Study
rhesus macaque
SARS-CoV-2
SARS-CoV-2 - growth & development
Spike Glycoprotein, Coronavirus - immunology
Viral Load - methods
Virus Replication - physiology
COVID-19
SARS-CoV-2
rhesus macaque
antibodies
nonhuman primates
antibody probes
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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 is needed. We developed a novel, fluorescently labeled, antibody-based 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 antibody-based probes to study SARS-CoV-2 infection dynamics in rhesus macaques.
AbstractList 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.
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 is needed. We developed a novel, fluorescently labeled, antibody-based 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 antibody-based probes to study SARS-CoV-2 infection dynamics in rhesus macaques.
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.
Author Potter, Elizabeth Lake
Madden, Patrick J
Lewis, Mark G
Midkiff, Cecily C
Carias, Ann M
Roy, Chad J
Dodson, Alan
Martin-Sancho, Laura
Hope, Thomas J
Chanda, Sumit K
Roederer, Mario
Blair, Robert V
Todd, John-Paul M
Veazey, Ronald S
Arif, Muhammad S
Becker, Mark E
Lorenzo-Redondo, Ramon
McRaven, Michael D
Xiao, Sixia
Aye, Pyone Pyone
Villinger, Francois J
Martinelli, Elena
AuthorAffiliation 2 Department of Medicine, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine , Chicago, IL , United States
4 Division of Comparative Pathology, Tulane National Primate Research Center , Covington, LA , United States
7 Bioqual Inc. , Rockville, MD , United States
5 Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD , United States
8 New Iberia Research Center, University of Louisiana-Lafayette , New Iberia, LA , United States
3 Center for Pathogen Genomics and Microbial Evolution, Northwestern University Institute for Global Health , Chicago, IL , United States
9 Division of Microbiology, Tulane National Primate Research Center , Covington, LA , United States
1 Department of Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University , Chicago, IL , United States
6 Immunity and Pathogenesis Program, Sanford Burnham Prebys Medical Discovery Institute , La Jolla, CA
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– name: 6 Immunity and Pathogenesis Program, Sanford Burnham Prebys Medical Discovery Institute , La Jolla, CA , United States
– name: 3 Center for Pathogen Genomics and Microbial Evolution, Northwestern University Institute for Global Health , Chicago, IL , United States
– name: 2 Department of Medicine, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine , Chicago, IL , United States
– name: 1 Department of Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University , Chicago, IL , United States
– name: 4 Division of Comparative Pathology, Tulane National Primate Research Center , Covington, LA , United States
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Copyright Copyright © 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.
Copyright © 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 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
Copyright_xml – notice: Copyright © 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.
– notice: Copyright © 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 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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Keywords COVID-19
SARS-CoV-2
rhesus macaque
antibodies
nonhuman primates
antibody probes
Language English
License Copyright © 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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This article was submitted to Viral Immunology, a section of the journal Frontiers in Immunology
Edited by: Krishanu Ray, University of Maryland, United States
Reviewed by: James J. Kobie, University of Alabama at Birmingham, United States; Li Liu, The University of Hong Kong, Hong Kong SAR, China
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Snippet Infection with the novel coronavirus, SARS-CoV-2, results in pneumonia and other respiratory symptoms as well as pathologies at diverse anatomical sites. An...
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StartPage 810047
SubjectTerms Animals
antibodies
Antibodies, Monoclonal - immunology
Antibodies, Neutralizing - immunology
Antibodies, Viral - immunology
antibody probes
Cell Line
COVID-19
COVID-19 - pathology
Disease Models, Animal
Fluorescent Antibody Technique - methods
Humans
Immunology
Lung - pathology
Lung - virology
Macaca mulatta
nonhuman primates
Proof of Concept Study
rhesus macaque
SARS-CoV-2
SARS-CoV-2 - growth & development
Spike Glycoprotein, Coronavirus - immunology
Viral Load - methods
Virus Replication - physiology
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Title Development of an In Vivo Probe to Track SARS-CoV-2 Infection in Rhesus Macaques
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