Respiratory disease in rhesus macaques inoculated with SARS-CoV-2

Munster, Vincent J.; Feldmann, Friederike; Williamson, Brandi N.; Doremalen, Neeltje van; Pérez-Pérez, Lizzette; Schulz, Jonathan; Meade-White, Kimberly; Okumura, Atsushi; Callison, Julie; Brumbaugh, Beniah; Avanzato, Victoria A.; Rosenke, Rebecca; Hanley, Patrick W.; Saturday, Greg; Scott, Dana; Fischer, Elizabeth R.; Wit, Emmie de

doi:10.1038/s41586-020-2324-7

Cited by 680 publications

(925 citation statements)

References 35 publications

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“…More specifically, the interaction of the viral spike (S) glycoprotein receptor binding domain with its hACE2 counterpart was examined 8,9 , and in some cases examined in vivo 10 . Productive SARS-CoV-2 infection was shown in non-human primates, which developed respiratory disease recapitulating moderate disease as observed in humans 11-14 . Mice are not naturally susceptible to SARS-CoV-2, but mouse-adapted virus strains have been developed and used in BALB/c mice 15,16 .…”

Section: Main Textmentioning

confidence: 84%

Age-dependent progression of SARS-CoV-2 infection in Syrian hamsters

Osterrieder

Bertzbach

Dietert

et al. 2020

Preprint

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22In late 2019, an outbreak of a severe respiratory disease caused by an emerging 23 coronavirus, SARS-CoV-2, resulted in high morbidity and mortality in infected humans 1 . 24Complete understanding of COVID-19, the multi-faceted disease caused by SARS-CoV-25 2, requires suitable small animal models, as does the development and evaluation of 26 vaccines and antivirals 2 . Because age-dependent differences of COVID-19 were identified 27 in humans 3 , we compared the course of SARS-CoV-2 infection in young and aged Syrian 28 hamsters. We show that virus replication in the upper and lower respiratory tract was 29 independent of the age of the animals. However, older hamsters exhibited more 30 pronounced and consistent weight loss. In situ hybridization in the lungs identified viral 31 RNA in bronchial epithelium, alveolar epithelial cells type I and II, and macrophages. 32Histopathology revealed clear age-dependent differences, with young hamsters launching 33 earlier and stronger immune cell influx than aged hamsters. The latter developed 34 conspicuous alveolar and perivascular edema, indicating vascular leakage. In contrast, 35we observed rapid lung recovery at day 14 after infection only in young hamsters. We 36propose that comparative assessment in young versus aged hamsters of SARS-CoV-2 37 vaccines and treatments may yield valuable information as this small-animal model 38 appears to mirror age-dependent differences in human patients.

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Section: Main Textmentioning

confidence: 84%

Age-dependent progression of SARS-CoV-2 infection in Syrian hamsters

Osterrieder

Bertzbach

Dietert

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…While working on SARS-CoV-2, rhesus macaques showed the establishment of SARS-CoV-2 infection with detection of high virus amount in oral-naso and rectal swabs. The apparent lesions of disease in lung radiographs and clinical signs lasting for up to 16 days proved the effectiveness of the model in studying the pathogenesis of this disease and aiding further in developing and testing vaccines and antivirals (Munster et al 2020).…”

Section: Animal Modelsmentioning

confidence: 97%

COVID-19: animals, veterinary and zoonotic links

Tiwari

Dhama

Sharun

et al. 2020

Veterinary Quarterly

246

237

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“…We next evaluated the efficacy of ChAdOx1 nCoV-19 in rhesus macaques, a non-human primate model that displays robust infection of upper and lower respiratory tract and virus shedding upon inoculation with SARS-CoV-2 6 . Twenty-eight days before challenge, 6 animals were vaccinated intramuscularly with 2.5 × 10 10 ChAdOx1 nCoV-19 virus particles each, half of the dose currently administered in human clinical trials.…”

Section: Immunogenicity In Micementioning

confidence: 99%

ChAdOx1 nCoV-19 vaccination prevents SARS-CoV-2 pneumonia in rhesus macaques

Doremalen

Lambe

Spencer

et al. 2020

Preprint

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274

284

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Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged in December 20191,2 and is responsible for the COVID-19 pandemic3. Vaccines are an essential countermeasure urgently needed to control the pandemic4. Here, we show that the adenovirus-vectored vaccine ChAdOx1 nCoV-19, encoding the spike protein of SARS-CoV-2, is immunogenic in mice, eliciting a robust humoral and cell-mediated response. This response was not Th2 dominated, as demonstrated by IgG subclass and cytokine expression profiling. A single vaccination with ChAdOx1 nCoV-19 induced a humoral and cellular immune response in rhesus macaques. We observed a significantly reduced viral load in bronchoalveolar lavage fluid and respiratory tract tissue of vaccinated animals challenged with SARS-CoV-2 compared with control animals, and no pneumonia was observed in vaccinated rhesus macaques. Importantly, no evidence of immune-enhanced disease following viral challenge in vaccinated animals was observed. ChAdOx1 nCoV-19 is currently under investigation in a phase I clinical trial. Safety, immunogenicity and efficacy against symptomatic PCR-positive COVID-19 disease will now be assessed in randomised controlled human clinical trials.

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Respiratory disease in rhesus macaques inoculated with SARS-CoV-2

Abstract: Cite this article as: Munster, V. J. et al. Respiratory disease in rhesus macaques inoculated with SARS-CoV-2. Nature

Cited by 680 publications

References 35 publications

Age-dependent progression of SARS-CoV-2 infection in Syrian hamsters

Age-dependent progression of SARS-CoV-2 infection in Syrian hamsters

COVID-19: animals, veterinary and zoonotic links

ChAdOx1 nCoV-19 vaccination prevents SARS-CoV-2 pneumonia in rhesus macaques

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