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

• Published in: Frontiers 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
• Language: English
• 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
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.810047

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.