SARS-CoV-2 infection of African green monkeys results in mild respiratory disease discernible by PET/CT imaging and shedding of infectious virus from both respiratory and gastrointestinal tracts.


Journal

PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921

Informations de publication

Date de publication:
09 2020
Historique:
received: 18 08 2020
accepted: 19 08 2020
revised: 05 10 2020
pubmed: 19 9 2020
medline: 21 10 2020
entrez: 18 9 2020
Statut: epublish

Résumé

Vaccines are urgently needed to combat the global coronavirus disease 2019 (COVID-19) pandemic, and testing of candidate vaccines in an appropriate non-human primate (NHP) model is a critical step in the process. Infection of African green monkeys (AGM) with a low passage human isolate of SARS-CoV-2 by aerosol or mucosal exposure resulted in mild clinical infection with a transient decrease in lung tidal volume. Imaging with human clinical-grade 18F-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET) co-registered with computed tomography (CT) revealed pulmonary lesions at 4 days post-infection (dpi) that resolved over time. Infectious virus was shed from both respiratory and gastrointestinal (GI) tracts in all animals in a biphasic manner, first between 2-7 dpi followed by a recrudescence at 14-21 dpi. Viral RNA (vRNA) was found throughout both respiratory and gastrointestinal systems at necropsy with higher levels of vRNA found within the GI tract tissues. All animals seroconverted simultaneously for IgM and IgG, which has also been documented in human COVID-19 cases. Young AGM represent an species to study mild/subclinical COVID-19 disease and with possible insights into live virus shedding. Future vaccine evaluation can be performed in AGM with correlates of efficacy being lung lesions by PET/CT, virus shedding, and tissue viral load.

Identifiants

pubmed: 32946524
doi: 10.1371/journal.ppat.1008903
pii: PPATHOGENS-D-20-01799
pmc: PMC7535860
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e1008903

Subventions

Organisme : NIH HHS
ID : P40 OD010965
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI060525
Pays : United States

Déclaration de conflit d'intérêts

The authors have declared that no competing interests exist.

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Auteurs

Amy L Hartman (AL)

Center for Vaccine Research, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
Department of Infectious Diseases and Microbiology, School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.

Sham Nambulli (S)

Center for Vaccine Research, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
Department of Microbiology and Molecular Genetics, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.

Cynthia M McMillen (CM)

Center for Vaccine Research, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
Department of Infectious Diseases and Microbiology, School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.

Alexander G White (AG)

Department of Microbiology and Molecular Genetics, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.

Natasha Louise Tilston-Lunel (NL)

Center for Vaccine Research, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
Department of Microbiology and Molecular Genetics, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.

Joseph R Albe (JR)

Center for Vaccine Research, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.

Emily Cottle (E)

Center for Vaccine Research, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.

Matthew D Dunn (MD)

Center for Vaccine Research, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.

L James Frye (LJ)

Department of Microbiology and Molecular Genetics, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.

Theron H Gilliland (TH)

Center for Vaccine Research, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.

Emily L Olsen (EL)

Center for Vaccine Research, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.

Katherine J O'Malley (KJ)

Center for Vaccine Research, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.

Madeline M Schwarz (MM)

Center for Vaccine Research, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
Department of Infectious Diseases and Microbiology, School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.

Jaime A Tomko (JA)

Department of Microbiology and Molecular Genetics, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.

Reagan C Walker (RC)

Division of Laboratory Animal Resources, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.

Mengying Xia (M)

Center for Vaccine Research, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.

Matthew S Hartman (MS)

Department of Radiology, Allegheny Health Network, Pittsburgh, Pennsylvania, United States of America.

Edwin Klein (E)

Division of Laboratory Animal Resources, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.

Charles A Scanga (CA)

Center for Vaccine Research, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
Department of Microbiology and Molecular Genetics, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.

JoAnne L Flynn (JL)

Center for Vaccine Research, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
Department of Microbiology and Molecular Genetics, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.

William B Klimstra (WB)

Center for Vaccine Research, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
Department of Immunology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.

Anita K McElroy (AK)

Center for Vaccine Research, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
Department of Pediatrics, Division of Pediatric Infectious Disease, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.

Douglas S Reed (DS)

Center for Vaccine Research, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
Department of Immunology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.

W Paul Duprex (WP)

Center for Vaccine Research, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
Department of Microbiology and Molecular Genetics, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.

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Classifications MeSH