ChAdOx1 nCoV-19 vaccination prevents SARS-CoV-2 pneumonia in rhesus macaques
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Abstract
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged in December 2019 1,2 and is responsible for the COVID-19 pandemic 3 . Vaccines are an essential countermeasure urgently needed to control the pandemic 4 . 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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SciScore for 10.1101/2020.05.13.093195: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: NHPs – Animal experiment approval was provided by the Institutional Animal Care and Use Committee (IACUC) at Rocky Mountain Laboratories. Randomization NHPs – 9 adult rhesus macaques (8M, 1F) were randomly divided into two groups of six and three animals. Blinding Animals were scored daily by the same person who was blinded to study group allocations using a standardized scoring sheet. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources The same calculation was used for diluting the sera to the same amounts of total IgG for further testing on different IgG … SciScore for 10.1101/2020.05.13.093195: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: NHPs – Animal experiment approval was provided by the Institutional Animal Care and Use Committee (IACUC) at Rocky Mountain Laboratories. Randomization NHPs – 9 adult rhesus macaques (8M, 1F) were randomly divided into two groups of six and three animals. Blinding Animals were scored daily by the same person who was blinded to study group allocations using a standardized scoring sheet. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources The same calculation was used for diluting the sera to the same amounts of total IgG for further testing on different IgG subclasses with anti-mouse IgG subclass-specific antibodies (Abcam). anti-mouse IgG subclass-specific antibodies ( Abcam) .suggested: NoneAntibodies were detected using affinity-purified polyclonal antibody peroxidase-labeled goat-anti-monkey IgG (Seracare, 074-11-021) in casein and TMB 2-component peroxidase substrate (Seracare, 5120-0047), developed for 5-10 min, and reaction was stopped using stop solution (Seracare, 5150-0021) and read at 450 nm. IgGsuggested: (Thermo Fisher Scientific Cat# A300-450A-M, RRID:AB_2779227)Specific anti-CoV immunoreactivity was detected using an in-house SARS-CoV-2 nucleocapsid protein rabbit antibody (Genscript) at a 1:1000 dilution. SARS-CoV-2 nucleocapsid proteinsuggested: (Bioss Cat# bsm-41414M, RRID:AB_2848129)Experimental Models: Cell Lines Sentences Resources The virus was rescued and propagated in T-Rex 293 HEK cells (Invitrogen) which repress antigen expression during virus propagation. HEKsuggested: CLS Cat# 300192/p777_HEK293, RRID:CVCL_0045)Virus propagation was performed in VeroE6 cells in DMEM supplemented with 2% fetal bovine serum, 1 mM L-glutamine, 50 U/ml penicillin and 50 μg/ml streptomycin. VeroE6suggested: JCRB Cat# JCRB1819, RRID:CVCL_YQ49)Experimental Models: Organisms/Strains Sentences Resources Study design animal experiments: Mice – Female BALB/cOlaHsd (BALB/c) (Envigo) and outbred Crl:CD1(ICR) (CD1) (Charles River) mice of at least 6 weeks of age, were immunized IM in the musculus tibialis with 6×109 VP of ChAdOx1 nCoV-19 unless otherwise stated. BALB/cOlaHsdsuggested: NoneBALB/csuggested: NoneSoftware and Algorithms Sentences Resources Sample acquisition was performed on a Fortessa (BD) and data analyzed in FlowJo v9 or FlowJo V10 (TreeStar). FlowJosuggested: (FlowJo, RRID:SCR_008520)Results from OddPub: Thank you for sharing your data.
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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