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

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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was not certified by peer review) is the author/funder. This article is a US Government work. It is not subject to copyright under 17 USC 105 The copyright holder for this preprint (which this version posted May 13, 2020. . https://doi.org/10.1101/2020.05.13.093195 doi: bioRxiv preprint NHPs. Any scoring associated with food was removed from final score. b. Viral load in BAL  and is also made available for use under a CC0 license. was not certified by peer review) is the author/funder. This article is a US Government work. It is not subject to copyright under 17 USC 105 The copyright holder for this preprint (which this version posted May 13, 2020. . https://doi.org/10.1101/2020.05.13.093195 doi: bioRxiv preprint 1 1 8 upregulation in IFN-γ at 1 DPI in ChAdOx1 nCoV-19 vaccinated animals, but not in control 1 1 9 animals. No significant differences were observed between ChAdOx1 nCoV-19 and control 1 2 0 animals for TNF-α , IL-2, IL-4, IL-6, and IL-10 (Extended Data Figure 2). At 7 days post inoculation, all animals were euthanized, and tissues were collected. None of the 1 2 4 vaccinated monkeys developed pulmonary pathology after inoculation with SARS-CoV-2. All 1 2 5 lungs were histologically normal and no evidence of viral pneumonia nor immune-enhanced 1 2 6 inflammatory disease was observed. In addition, no SARS-CoV-2 antigen was detected by  Immunohistochemistry demonstrated viral antigen in type I and II pneumocytes, as well as in  and is also made available for use under a CC0 license.
was not certified by peer review) is the author/funder. This article is a US Government work. It is not subject to copyright under 17 USC 105 The copyright holder for this preprint (which this version posted May 13, 2020. . https://doi.org/10.1101/2020.05.13.093195 doi: bioRxiv preprint  and is also made available for use under a CC0 license. was not certified by peer review) is the author/funder. This article is a US Government work. It is not subject to copyright under 17 USC 105 The copyright holder for this preprint (which this version posted May 13, 2020. . https://doi.org/10.1101/2020.05.13.093195 doi: bioRxiv preprint below limits of detection in two vaccinated animals. Viral sgRNA was detected in lung tissue 1 5 2 obtained from 1 out of 6 vaccinated animals (p<0.0001, Figure 3d). Viral gRNA could be 1 5 3 detected in other tissues but was low in both groups (Extended Data Figure 3). Here, we showed that a single vaccination with ChAdOx1 nCoV-19 is effective in preventing  Several preclinical studies of vaccines against SARS-CoV-1 resulted in immunopathology after 1 6 7 vaccination and challenge, with more severe disease in vaccinated animals than in controls 8-10 . Importantly, we did not see any evidence of immune-enhanced disease in vaccinated animals. The immune response was not skewed towards a Th2 response in mice nor in NHPs, there was with ChAdOx1 nCoV-19 on April 23, 2020. As of May 13, 2020, more than 1000 volunteers 1 7 4 and is also made available for use under a CC0 license.
was not certified by peer review) is the author/funder. This article is a US Government work. It is not subject to copyright under 17 USC 105 The copyright holder for this preprint (which this version posted May 13, 2020. . https://doi.org/10.1101/2020.05.13.093195 doi: bioRxiv preprint have participated in the clinical trials. This study is thus an important step towards the 1 7 5 development of a safe and efficacious SARS-CoV-2 vaccine. vaccine against severe acute respiratory syndrome is associated with enhanced hepatitis in ferrets.    hours/12-hours). and is also made available for use under a CC0 license.
was not certified by peer review) is the author/funder. This article is a US Government work. It is not subject to copyright under 17 USC 105 The copyright holder for this preprint (which this version posted May 13, 2020. . https://doi.org/10.1101/2020 following the basic principles and guidelines in the NIH Guide for the Care and Use of Laboratory conditions. All sample inactivation was performed according to IBC approved standard operating 2 2 0 procedures for removal of specimens from high containment. The spike protein of SARS-CoV-2 (Genbank accession number YP_009724390.1), the surface hexon immunostaining assay and viral particles calculated based on spectrophotometry 12,13 . and is also made available for use under a CC0 license.
was not certified by peer review) is the author/funder. This article is a US Government work. It is not subject to copyright under 17 USC 105 The copyright holder for this preprint (which this version posted May 13, 2020. mice of at least 6 weeks of age, were immunized IM in the musculus tibialis with 6x10 9 VP of ChAdOx1 2 4 0 nCoV-19 unless otherwise stated.

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Virus neutralization assay 2 6 3 and is also made available for use under a CC0 license.
was not certified by peer review) is the author/funder. This article is a US Government work. It is not subject to copyright under 17 USC 105 The copyright holder for this preprint (which this version posted May 13, 2020. . https://doi.org/10.1101/2020.05.13.093195 doi: bioRxiv preprint