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ChAdOx1 nCoV-19 vaccination prevents SARS-CoV-2 pneumonia in rhesus macaques.
bioRxiv. 2020 May 13B

Abstract

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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Authors+Show Affiliations

van Doremalen N
Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
Lambe T
The Jenner Institute, University of Oxford, Oxford, UK.
Spencer A
The Jenner Institute, University of Oxford, Oxford, UK.
Belij-Rammerstorfer S
The Jenner Institute, University of Oxford, Oxford, UK.
Purushotham JN
Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA. The Jenner Institute, University of Oxford, Oxford, UK.
Port JR
Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
Avanzato V
Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
Bushmaker T
Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
Flaxman A
The Jenner Institute, University of Oxford, Oxford, UK.
Ulaszewska M
The Jenner Institute, University of Oxford, Oxford, UK.
Feldmann F
Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
Allen ER
The Jenner Institute, University of Oxford, Oxford, UK.
Sharpe H
The Jenner Institute, University of Oxford, Oxford, UK.
Schulz J
Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
Holbrook M
Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
Okumura A
Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
Meade-White K
Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
Pérez-Pérez L
Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
Bissett C
The Jenner Institute, University of Oxford, Oxford, UK.
Gilbride C
The Jenner Institute, University of Oxford, Oxford, UK.
Williamson BN
Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
Rosenke R
Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
Long D
Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
Ishwarbhai A
The Jenner Institute, University of Oxford, Oxford, UK.
Kailath R
The Jenner Institute, University of Oxford, Oxford, UK.
Rose L
The Jenner Institute, University of Oxford, Oxford, UK.
Morris S
The Jenner Institute, University of Oxford, Oxford, UK.
Powers C
The Jenner Institute, University of Oxford, Oxford, UK.
Lovaglio J
Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
Hanley PW
Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
Scott D
Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
Saturday G
Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
de Wit E
Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
Gilbert SC
The Jenner Institute, University of Oxford, Oxford, UK.
Munster VJ
Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.

Pub Type(s)

Preprint

Language

eng

PubMed ID

32511340

Clinical Trial Links

Phase III Double-blind, Placebo-controlled Study of AZD1222 for the Prevention of COVID-19 in Adults

Citation

van Doremalen, Neeltje, et al. "ChAdOx1 nCoV-19 Vaccination Prevents SARS-CoV-2 Pneumonia in Rhesus Macaques." BioRxiv : the Preprint Server for Biology, 2020.
van Doremalen N, Lambe T, Spencer A, et al. ChAdOx1 nCoV-19 vaccination prevents SARS-CoV-2 pneumonia in rhesus macaques. bioRxiv. 2020.
van Doremalen, N., Lambe, T., Spencer, A., Belij-Rammerstorfer, S., Purushotham, J. N., Port, J. R., Avanzato, V., Bushmaker, T., Flaxman, A., Ulaszewska, M., Feldmann, F., Allen, E. R., Sharpe, H., Schulz, J., Holbrook, M., Okumura, A., Meade-White, K., Pérez-Pérez, L., Bissett, C., ... Munster, V. J. (2020). ChAdOx1 nCoV-19 vaccination prevents SARS-CoV-2 pneumonia in rhesus macaques. BioRxiv : the Preprint Server for Biology. https://doi.org/10.1101/2020.05.13.093195
van Doremalen N, et al. ChAdOx1 nCoV-19 Vaccination Prevents SARS-CoV-2 Pneumonia in Rhesus Macaques. bioRxiv. 2020 May 13; PubMed PMID: 32511340.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - ChAdOx1 nCoV-19 vaccination prevents SARS-CoV-2 pneumonia in rhesus macaques. AU - van Doremalen,Neeltje, AU - Lambe,Teresa, AU - Spencer,Alexandra, AU - Belij-Rammerstorfer,Sandra, AU - Purushotham,Jyothi N, AU - Port,Julia R, AU - Avanzato,Victoria, AU - Bushmaker,Trenton, AU - Flaxman,Amy, AU - Ulaszewska,Marta, AU - Feldmann,Friederike, AU - Allen,Elizabeth R, AU - Sharpe,Hannah, AU - Schulz,Jonathan, AU - Holbrook,Myndi, AU - Okumura,Atsushi, AU - Meade-White,Kimberly, AU - Pérez-Pérez,Lizzette, AU - Bissett,Cameron, AU - Gilbride,Ciaran, AU - Williamson,Brandi N, AU - Rosenke,Rebecca, AU - Long,Dan, AU - Ishwarbhai,Alka, AU - Kailath,Reshma, AU - Rose,Louisa, AU - Morris,Susan, AU - Powers,Claire, AU - Lovaglio,Jamie, AU - Hanley,Patrick W, AU - Scott,Dana, AU - Saturday,Greg, AU - de Wit,Emmie, AU - Gilbert,Sarah C, AU - Munster,Vincent J, Y1 - 2020/05/13/ PY - 2020/6/9/entrez PY - 2020/6/9/pubmed PY - 2020/6/9/medline JF - bioRxiv : the preprint server for biology JO - bioRxiv N2 - 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. UR - https://www.unboundmedicine.com/medline/citation/32511340/ChAdOx1_nCoV_19_vaccination_prevents_SARS_CoV_2_pneumonia_in_rhesus_macaques_ DB - PRIME DP - Unbound Medicine ER -