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

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

doi:10.3389/fimmu.2021.810047

Cited by 4 publications

(3 citation statements)

References 57 publications

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“…As we previously reported (Madden et al), studies in SARS-CoV-2 infected rhesus macaques were consistent with the intravenously (IV) injected probe being able to associate with and accumulate in SARS-CoV-2 infected cells, as also seen in tissue culture 24 . Based on the ability of the fluorophore labeled CR3022-F(ab')2 to reveal sites of SARS-CoV-2 infection within macaque tissues, we extended these studies to utilize a [ 64 Cu] -DOTA-labelled CR3022-F(ab')2 probe followed by detection in PET/CT scan.…”

Section: Introductionsupporting

confidence: 88%

“…It can be used to determine the precise location of infected cells in radioactive probe-guided necropsy. We have previously reported the early development of an in vivo antibody-based probe against SARS-CoV-2 utilizing fluorescent tagging of the F(ab')2 of the anti-spike IgG CR3022 24 . CR3022 was one of the first monoclonal antibodies identified that bound tightly to SARS-CoV-2.…”

Section: Introductionmentioning

confidence: 99%

“…We have previously reported the early development of an in vivo antibody-based probe against SARS-CoV-2 utilizing fluorescent tagging of the F(ab')2 of the anti-spike IgG CR3022 24 .…”

Section: Introductionmentioning

confidence: 99%

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An immunoPET probe to SARS-CoV-2 reveals early infection of the male genital tract in rhesus macaques

Madden

Thomas

Blair

et al. 2022

Preprint

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Because of the recognized systemic nature of SARS-CoV-2 infection, a non-invasive and unbiased method is needed to clarify its spatiotemporal dynamics in vivo after transmission. We recently developed a probe based on the anti-SARS-CoV-2 spike antibody CR3022 to study SARS-CoV-2 pathogenesis in vivo. Herein, we describe its use in immunoPET to investigate SARS-CoV-2 infection of rhesus macaques. Using PET/CT imaging of macaques at different times post-SARS-CoV-2 inoculation, we demonstrate that the 64Cu-labelled CR3022-F(ab′)2 probe targeting the spike protein of SARS-CoV-2 can be used to study the dynamics of infection within the respiratory tract and uncover novel sites of infection. Differences in lung pathology between infection with the WA1 isolate and the delta variant were readily observed using immunoPET and corroborated CT lung pathology. The ability of the probe to illuminate lung-associated pathology demonstrates its specificity and function to detect infection in PET scan. The 64Cu-CR3022-probe also demonstrated dynamic changes occurring between 1- and 2-weeks post-infection. Remarkably, a robust signal was seen in the male genital tract (MGT) of all three animals studied. Infection of the MGT was validated by immunofluorescence imaging of infected cells in the testicular and penile tissue and severe pathology was observed in the testes of one animal at 2-weeks post-infection. The results presented here underscore the utility of using immunoPET to study the dynamics of SARS-CoV-2 infection to understand its pathogenicity and discover new anatomical sites of viral replication. We provide direct evidence for SARS-CoV-2 infection of the MGT in rhesus macaques revealing the possible pathologic outcomes of viral replication at these sites.

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Section: Introductionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

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An immunoPET probe to SARS-CoV-2 reveals early infection of the male genital tract in rhesus macaques

Madden

Thomas

Blair

et al. 2022

Preprint

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Imaging the immune sequelae of infection with SARS‐CoV‐2 in nonhuman primates by using two nanobody PET‐tracers

Koopman,

Verhoeven,

Mooij

et al. 2024

Journal of Medical Virology

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Infection with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) impacts multiple anatomical sites. Whether this is due to the virus itself or is a secondary effect caused by the influx and activation of immune cells is not known. Positron emission tomography (PET) with immunoglobulins can provide insights into which sites and cells are activated in a living animal. Our aim is to use two nanobodies as tools to monitor (1) the distribution of antigen presenting cells (APC) by virtue of their Mafa‐DR expression profile, (2) virus‐infected cells and viral particles using a nanobody against the SARS‐CoV‐2 spike protein. Two [89Zr]‐labeled nanobodies that target the SARS‐CoV‐2 spike protein and major histocompatability complex (MHC) class II antigens (Mafa‐DR), respectively, are used to monitor their distribution during an experimental SARS‐CoV‐2 infection in a nonhuman primate model. Scans are obtained before infection and on Day 3 and 10 post infection (pi) in two macaques each. The [89Zr]anti‐SARS‐CoV‐2 spike nanobody localized to SARS‐CoV‐2‐associated lung lesions and the nasal mucosa, while the [89Zr]anti‐human leukocyte antigen (HLA)‐DR nanobody was predominantly found in non‐affected lung tissue after infection. We also detected, pi, upregulation of the Mafa‐DR signal, indicative of recruitment of professional APCs, in the superior sagittal sinus. [89Zr]‐labeled nanobodies show recruitment of macrophages/monocytes in non‐lesional lung tissue in cynomolgus macaques after experimental infection with SARS‐CoV‐2, as well as accumulation of the spike protein in both lung lesions and the nasal mucosa during infection. These results show the possibility of in vivo monitoring the quality and quantity of immune responses during the initial stages of an infection.

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Transcriptomic approaches in COVID-19: From infection to vaccines

Gardinassi¹,

Souza²,

Lima³

et al. 2023

Omics Approaches and Technologies in COVID-19

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

Cited by 4 publications

References 57 publications

An immunoPET probe to SARS-CoV-2 reveals early infection of the male genital tract in rhesus macaques

An immunoPET probe to SARS-CoV-2 reveals early infection of the male genital tract in rhesus macaques

Imaging the immune sequelae of infection with SARS‐CoV‐2 in nonhuman primates by using two nanobody PET‐tracers

Transcriptomic approaches in COVID-19: From infection to vaccines

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