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

Neeltje van Doremalen, Teresa Lambe, Alexandra Spencer, Sandra Belij-Rammerstorfer, Jyothi N. Purushotham, Julia R. Port, Victoria Avanzato, Trenton Bushmaker, Amy Flaxman, Marta Ulaszewska, Friederike Feldmann, Elizabeth R. Allen, Hannah Sharpe, Jonathan Schulz, Myndi Holbrook, Atsushi Okumura, Kimberly Meade-White, Lizzette Pérez-Pérez, Cameron Bissett, Ciaran Gilbride, Brandi N. Williamson, Rebecca Rosenke, Dan Long, Alka Ishwarbhai, Reshma Kailath, Louisa Rose, Susan Morris, Claire Powers, Jamie Lovaglio, Patrick W. Hanley, Dana Scott, Greg Saturday, Emmie de Wit, View ORCID ProfileSarah C. Gilbert, View ORCID ProfileVincent J. Munster
doi: https://doi.org/10.1101/2020.05.13.093195
Neeltje van Doremalen
1Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA
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Teresa Lambe
2The Jenner Institute, University of Oxford, Oxford, UK
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Alexandra Spencer
2The Jenner Institute, University of Oxford, Oxford, UK
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Sandra Belij-Rammerstorfer
2The Jenner Institute, University of Oxford, Oxford, UK
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Jyothi N. Purushotham
1Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA
2The Jenner Institute, University of Oxford, Oxford, UK
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Julia R. Port
1Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA
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Victoria Avanzato
1Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA
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Trenton Bushmaker
1Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA
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Amy Flaxman
2The Jenner Institute, University of Oxford, Oxford, UK
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Marta Ulaszewska
2The Jenner Institute, University of Oxford, Oxford, UK
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Friederike Feldmann
3Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA
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Elizabeth R. Allen
2The Jenner Institute, University of Oxford, Oxford, UK
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Hannah Sharpe
2The Jenner Institute, University of Oxford, Oxford, UK
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Jonathan Schulz
1Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA
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Myndi Holbrook
1Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA
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Atsushi Okumura
1Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA
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Kimberly Meade-White
1Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA
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Lizzette Pérez-Pérez
1Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA
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Cameron Bissett
2The Jenner Institute, University of Oxford, Oxford, UK
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Ciaran Gilbride
2The Jenner Institute, University of Oxford, Oxford, UK
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Brandi N. Williamson
1Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA
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Rebecca Rosenke
3Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA
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Dan Long
3Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA
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Alka Ishwarbhai
2The Jenner Institute, University of Oxford, Oxford, UK
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Reshma Kailath
2The Jenner Institute, University of Oxford, Oxford, UK
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Louisa Rose
2The Jenner Institute, University of Oxford, Oxford, UK
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Susan Morris
2The Jenner Institute, University of Oxford, Oxford, UK
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Claire Powers
2The Jenner Institute, University of Oxford, Oxford, UK
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Jamie Lovaglio
3Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA
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Patrick W. Hanley
3Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA
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Dana Scott
3Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA
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Greg Saturday
3Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA
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Emmie de Wit
1Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA
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Sarah C. Gilbert
2The Jenner Institute, University of Oxford, Oxford, UK
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  • ORCID record for Sarah C. Gilbert
  • For correspondence: vincent.munster@nih.gov sarah.gilbert@ndm.ox.ac.uk
Vincent J. Munster
1Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA
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  • ORCID record for Vincent J. Munster
  • For correspondence: vincent.munster@nih.gov sarah.gilbert@ndm.ox.ac.uk
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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.

Competing Interest Statement

SCG is a board member of Vaccitech and named as an inventor on a patent covering use of ChAdOx1-vectored vaccines and a patent application covering a SARS-CoV-2 (nCoV-19) vaccine. Teresa Lambe is named as an inventor on a patent application covering a SARS-CoV-2 (nCoV-19) vaccine. The remaining authors declare no competing interests.

Footnotes

  • ↵* Joint first authors

  • ↵# Joint senior authors

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.
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ChAdOx1 nCoV-19 vaccination prevents SARS-CoV-2 pneumonia in rhesus macaques
Neeltje van Doremalen, Teresa Lambe, Alexandra Spencer, Sandra Belij-Rammerstorfer, Jyothi N. Purushotham, Julia R. Port, Victoria Avanzato, Trenton Bushmaker, Amy Flaxman, Marta Ulaszewska, Friederike Feldmann, Elizabeth R. Allen, Hannah Sharpe, Jonathan Schulz, Myndi Holbrook, Atsushi Okumura, Kimberly Meade-White, Lizzette Pérez-Pérez, Cameron Bissett, Ciaran Gilbride, Brandi N. Williamson, Rebecca Rosenke, Dan Long, Alka Ishwarbhai, Reshma Kailath, Louisa Rose, Susan Morris, Claire Powers, Jamie Lovaglio, Patrick W. Hanley, Dana Scott, Greg Saturday, Emmie de Wit, Sarah C. Gilbert, Vincent J. Munster
bioRxiv 2020.05.13.093195; doi: https://doi.org/10.1101/2020.05.13.093195
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ChAdOx1 nCoV-19 vaccination prevents SARS-CoV-2 pneumonia in rhesus macaques
Neeltje van Doremalen, Teresa Lambe, Alexandra Spencer, Sandra Belij-Rammerstorfer, Jyothi N. Purushotham, Julia R. Port, Victoria Avanzato, Trenton Bushmaker, Amy Flaxman, Marta Ulaszewska, Friederike Feldmann, Elizabeth R. Allen, Hannah Sharpe, Jonathan Schulz, Myndi Holbrook, Atsushi Okumura, Kimberly Meade-White, Lizzette Pérez-Pérez, Cameron Bissett, Ciaran Gilbride, Brandi N. Williamson, Rebecca Rosenke, Dan Long, Alka Ishwarbhai, Reshma Kailath, Louisa Rose, Susan Morris, Claire Powers, Jamie Lovaglio, Patrick W. Hanley, Dana Scott, Greg Saturday, Emmie de Wit, Sarah C. Gilbert, Vincent J. Munster
bioRxiv 2020.05.13.093195; doi: https://doi.org/10.1101/2020.05.13.093195

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