ChAdOx1 nCoV-19 vaccine prevents SARS-CoV-2 pneumonia in rhesus macaques.
ChAdOx1 nCoV-19 vaccine prevents SARS-CoV-2 pneumonia in rhesus macaques.
复制标题
Chadox1 NCOV-19疫苗可防止恒河猕猴中的SARS-COV-2肺炎。
DOI：
10.1038/s41586-020-2608-y
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发表时间：
2020-10
期刊：
影响因子：
64.8
通讯作者：
Munster VJ
中科院分区：
文献类型：
--
作者：
van Doremalen N;Lambe T;Spencer A;Belij-Rammerstorfer S;Purushotham JN;Port JR;Avanzato VA;Bushmaker T;Flaxman A;Ulaszewska M;Feldmann F;Allen ER;Sharpe H;Schulz J;Holbrook M;Okumura A;Meade-White K;Pérez-Pérez L;Edwards NJ;Wright D;Bissett C;Gilbride C;Williamson BN;Rosenke R;Long D;Ishwarbhai A;Kailath R;Rose L;Morris S;Powers C;Lovaglio J;Hanley PW;Scott D;Saturday G;de Wit E;Gilbert SC;Munster VJ
严重急性呼吸系统综合征冠状病毒2型（SARS-CoV-2）于2019年12月出现，并导致COVID-19大流行。疫苗是控制这一流行病迫切需要的基本对策。在这里，我们表明，腺病毒载体的疫苗ChAdOx 1 nCoV-19，编码的刺突蛋白的SARS冠状病毒-2，是免疫原性的小鼠，引发了强大的体液和细胞介导的反应。这种反应主要是Th 1，如IgG亚类和细胞因子表达谱所示。ChAdOx 1 nCoV-19疫苗接种（仅初免和初免-加强方案）在恒河猴中诱导平衡的Th 1/Th 2体液和细胞免疫应答。我们观察到与对照动物相比，SARS-CoV-2激发的接种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著降低，并且在接种疫苗的动物中没有观察到肺炎。然而，接种组动物和对照组动物之间的鼻散毒无差异。重要的是，在接种疫苗的动物中未观察到病毒攻击后免疫增强疾病的证据。ChAdOx 1 nCoV-19对症状性PCR阳性COVID-19疾病的安全性、免疫原性和有效性现在将在随机对照人体临床试验中进行评估。
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged in December 2019 and is responsible for the COVID-19 pandemic. Vaccines are an essential countermeasure urgently needed to control the pandemic. 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 predominantly Th1, as demonstrated by IgG subclass and cytokine expression profiling. Vaccination with ChAdOx1 nCoV-19 (prime-only and prime-boost regimen) induced a balanced Th1/Th2 humoral and cellular immune response in rhesus macaques. We observed a significantly reduced viral load in bronchoalveolar lavage fluid and lower respiratory tract tissue of vaccinated rhesus macaques challenged with SARS-CoV-2 compared with control animals, and no pneumonia was observed in vaccinated animals. However, there was no difference in nasal shedding between vaccinated and control animals. Importantly, no evidence of immune-enhanced disease following viral challenge in vaccinated animals was observed. Safety, immunogenicity and efficacy of ChAdOx1 nCoV-19 against symptomatic PCR-positive COVID-19 disease will now be assessed in randomised controlled human clinical trials.
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