4.8 Article

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

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NATURE
卷 586, 期 7830, 页码 578-+

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NATURE PORTFOLIO
DOI: 10.1038/s41586-020-2608-y

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资金

  1. Intramural Research Program of the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH) [1ZIAAI001179-01]
  2. Department of Health and Social Care
  3. NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [ZICAI001330, ZIGAI001048, ZIAAI001288, ZIAAI001289] Funding Source: NIH RePORTER
  4. EPSRC [EP/R013756/1] Funding Source: UKRI
  5. MRC [MC_PC_19055] Funding Source: UKRI

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The ChAdOx1 nCoV-19 vaccine against SARS-CoV-2 induces an immune response in rhesus macaques and leads to reduced SARS-CoV-2 viral loads in respiratory tissues and an absence of pneumonia, but not to a reduction in nasal virus shedding, compared with unvaccinated animals. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019(1,2)and is responsible for the coronavirus disease 2019 (COVID-19) pandemic(3). Vaccines are an essential countermeasure and are urgently needed to control the pandemic(4). 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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