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ChAdOx1 nCoV-19 vaccine prevents SARS-CoV-2 pneumonia in rhesus macaques
Nature ( IF 64.8 ) Pub Date : 2020-07-30 , DOI: 10.1038/s41586-020-2608-y
Neeltje van Doremalen 1 , Teresa Lambe 2 , Alexandra Spencer 2 , Sandra Belij-Rammerstorfer 2 , Jyothi N Purushotham 1, 2 , Julia R Port 1 , Victoria A Avanzato 1 , Trenton Bushmaker 1 , Amy Flaxman 2 , Marta Ulaszewska 2 , Friederike Feldmann 3 , Elizabeth R Allen 2 , Hannah Sharpe 2 , Jonathan Schulz 1 , Myndi Holbrook 1 , Atsushi Okumura 1 , Kimberly Meade-White 1 , Lizzette Pérez-Pérez 1 , Nick J Edwards 2 , Daniel Wright 2 , Cameron Bissett 2 , Ciaran Gilbride 2 , Brandi N Williamson 1 , Rebecca Rosenke 3 , Dan Long 3 , Alka Ishwarbhai 2 , Reshma Kailath 2 , Louisa Rose 2 , Susan Morris 2 , Claire Powers 2 , Jamie Lovaglio 3 , Patrick W Hanley 3 , Dana Scott 3 , Greg Saturday 3 , Emmie de Wit 1 , Sarah C Gilbert 2 , Vincent J Munster 1
Affiliation  

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. 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.

中文翻译:

ChAdOx1 nCoV-19 疫苗可预防恒河猴的 SARS-CoV-2 肺炎

严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 于 2019 年 12 月出现 1, 2 并导致 2019 年冠状病毒病 (COVID-19) 大流行 3 。疫苗是一项重要的对策,是控制大流行病的迫切需要 4 。在这里,我们展示了基于腺病毒载体的疫苗 ChAdOx1 nCoV-19,它编码 SARS-CoV-2 的刺突蛋白,在小鼠中具有免疫原性,并引发强烈的体液和细胞介导的反应。这种反应主要由 1 型 T 辅助细胞介导,IgG 亚类的分析和细胞因子的表达证明了这一点。接种 ChAdOx1 nCoV-19(使用仅初免或初免-加强方案)在恒河猴中诱导了 1 型和 2 型 T 辅助细胞的平衡体液和细胞免疫反应。我们观察到,与对照动物相比,接种过 SARS-CoV-2 疫苗的恒河猴的支气管肺泡灌洗液和下呼吸道组织中的病毒载量显着降低,并且在接种过 SARS-CoV-2 感染的动物中未观察到肺炎. 但是,接种疫苗的猕猴和感染 SARS-CoV-2 的对照猕猴之间的鼻腔脱落没有差异。值得注意的是,我们没有发现在接种疫苗的 SARS-CoV-2 感染动物进行病毒攻击后出现免疫增强疾病的证据。现在将在人体随机对照临床试验中评估 ChAdOx1 nCoV-19 对症状性 PCR 阳性 COVID-19 疾病的安全性、免疫原性和疗效概况。
更新日期:2020-07-30
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