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ChAdOx1 nCoV-19 vaccine prevents SARS-CoV-2 pneumonia in rhesus macaques.
Nature. 2020 10; 586(7830):578-582.Nat

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 20191,2 and is responsible for the coronavirus disease 2019 (COVID-19) pandemic3. Vaccines are an essential countermeasure and are urgently needed to control the pandemic4. Here we show that the adenovirus-vector-based vaccine ChAdOx1 nCoV-19, which encodes the spike protein of SARS-CoV-2, is immunogenic in mice and elicites a robust humoral and cell-mediated response. This response was predominantly mediated by type-1 T helper cells, as demonstrated by the profiling of the IgG subclass and the expression of cytokines. Vaccination with ChAdOx1 nCoV-19 (using either a prime-only or a prime-boost regimen) induced a balanced humoral and cellular immune response of type-1 and type-2 T helper cells in rhesus macaques. We observed a significantly reduced viral load in the bronchoalveolar lavage fluid and lower respiratory tract tissue of vaccinated rhesus macaques that were challenged with SARS-CoV-2 compared with control animals, and no pneumonia was observed in vaccinated SARS-CoV-2-infected animals. However, there was no difference in nasal shedding between vaccinated and control SARS-CoV-2-infected macaques. Notably, we found no evidence of immune-enhanced disease after viral challenge in vaccinated SARS-CoV-2-infected animals. The safety, immunogenicity and efficacy profiles of ChAdOx1 nCoV-19 against symptomatic PCR-positive COVID-19 disease will now be assessed in randomized controlled clinical trials in humans.

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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 VA
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.
Edwards NJ
The Jenner Institute, University of Oxford, Oxford, UK.
Wright D
The Jenner Institute, University of Oxford, Oxford, UK.
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. sarah.gilbert@ndm.ox.ac.uk.
Munster VJ
Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA. vincent.munster@nih.gov.

MeSH

AdenoviridaeAnimalsBetacoronavirusBronchoalveolar Lavage FluidCOVID-19COVID-19 VaccinesCoronavirus InfectionsCytokinesDisease Models, AnimalFemaleImmunity, CellularImmunity, HumoralImmunoglobulin GLungMacaca mulattaMaleMicePandemicsPneumonia, ViralSARS-CoV-2Spike Glycoprotein, CoronavirusTh1 CellsVaccinationViral LoadViral Vaccines

Pub Type(s)

Journal Article
Research Support, N.I.H., Intramural

Language

eng

PubMed ID

32731258

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 Vaccine Prevents SARS-CoV-2 Pneumonia in Rhesus Macaques." Nature, vol. 586, no. 7830, 2020, pp. 578-582.
van Doremalen N, Lambe T, Spencer A, et al. ChAdOx1 nCoV-19 vaccine prevents SARS-CoV-2 pneumonia in rhesus macaques. Nature. 2020;586(7830):578-582.
van Doremalen, N., Lambe, T., Spencer, A., Belij-Rammerstorfer, S., Purushotham, J. N., Port, J. R., Avanzato, V. A., 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., Edwards, N. J., ... Munster, V. J. (2020). ChAdOx1 nCoV-19 vaccine prevents SARS-CoV-2 pneumonia in rhesus macaques. Nature, 586(7830), 578-582. https://doi.org/10.1038/s41586-020-2608-y
van Doremalen N, et al. ChAdOx1 nCoV-19 Vaccine Prevents SARS-CoV-2 Pneumonia in Rhesus Macaques. Nature. 2020;586(7830):578-582. PubMed PMID: 32731258.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - ChAdOx1 nCoV-19 vaccine 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 A, 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 - Edwards,Nick J, AU - Wright,Daniel, 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 - 2020/07/30/ PY - 2020/05/13/received PY - 2020/07/24/accepted PY - 2020/7/31/pubmed PY - 2020/10/30/medline PY - 2020/7/31/entrez SP - 578 EP - 582 JF - Nature JO - Nature VL - 586 IS - 7830 N2 - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 20191,2 and is responsible for the coronavirus disease 2019 (COVID-19) pandemic3. Vaccines are an essential countermeasure and are urgently needed to control the pandemic4. Here we show that the adenovirus-vector-based vaccine ChAdOx1 nCoV-19, which encodes the spike protein of SARS-CoV-2, is immunogenic in mice and elicites a robust humoral and cell-mediated response. This response was predominantly mediated by type-1 T helper cells, as demonstrated by the profiling of the IgG subclass and the expression of cytokines. Vaccination with ChAdOx1 nCoV-19 (using either a prime-only or a prime-boost regimen) induced a balanced humoral and cellular immune response of type-1 and type-2 T helper cells in rhesus macaques. We observed a significantly reduced viral load in the bronchoalveolar lavage fluid and lower respiratory tract tissue of vaccinated rhesus macaques that were challenged with SARS-CoV-2 compared with control animals, and no pneumonia was observed in vaccinated SARS-CoV-2-infected animals. However, there was no difference in nasal shedding between vaccinated and control SARS-CoV-2-infected macaques. Notably, we found no evidence of immune-enhanced disease after viral challenge in vaccinated SARS-CoV-2-infected animals. The safety, immunogenicity and efficacy profiles of ChAdOx1 nCoV-19 against symptomatic PCR-positive COVID-19 disease will now be assessed in randomized controlled clinical trials in humans. SN - 1476-4687 UR - https://www.unboundmedicine.com/medline/citation/32731258/ChAdOx1_nCoV_19_vaccine_prevents_SARS_CoV_2_pneumonia_in_rhesus_macaques_ L2 - https://doi.org/10.1038/s41586-020-2608-y DB - PRIME DP - Unbound Medicine ER -