ChAdOx1 nCoV-19 vaccine 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 A. 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, Nick J. Edwards, Daniel Wright, 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 () and Vincent J. Munster ()
Additional contact information
Neeltje van Doremalen: Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Teresa Lambe: University of Oxford
Alexandra Spencer: University of Oxford
Sandra Belij-Rammerstorfer: University of Oxford
Jyothi N. Purushotham: Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Julia R. Port: Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Victoria A. Avanzato: Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Trenton Bushmaker: Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Amy Flaxman: University of Oxford
Marta Ulaszewska: University of Oxford
Friederike Feldmann: National Institute of Allergy and Infectious Diseases, National Institutes of Health
Elizabeth R. Allen: University of Oxford
Hannah Sharpe: University of Oxford
Jonathan Schulz: Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Myndi Holbrook: Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Atsushi Okumura: Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Kimberly Meade-White: Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Lizzette Pérez-Pérez: Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Nick J. Edwards: University of Oxford
Daniel Wright: University of Oxford
Cameron Bissett: University of Oxford
Ciaran Gilbride: University of Oxford
Brandi N. Williamson: Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Rebecca Rosenke: National Institute of Allergy and Infectious Diseases, National Institutes of Health
Dan Long: National Institute of Allergy and Infectious Diseases, National Institutes of Health
Alka Ishwarbhai: University of Oxford
Reshma Kailath: University of Oxford
Louisa Rose: University of Oxford
Susan Morris: University of Oxford
Claire Powers: University of Oxford
Jamie Lovaglio: National Institute of Allergy and Infectious Diseases, National Institutes of Health
Patrick W. Hanley: National Institute of Allergy and Infectious Diseases, National Institutes of Health
Dana Scott: National Institute of Allergy and Infectious Diseases, National Institutes of Health
Greg Saturday: National Institute of Allergy and Infectious Diseases, National Institutes of Health
Emmie de Wit: Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Sarah C. Gilbert: University of Oxford
Vincent J. Munster: Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health

Nature, 2020, vol. 586, issue 7830, 578-582

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41586-020-2608-y

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