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Antibody-mediated protection against MERS-CoV in the murine model

机译:抗体介导对小鼠模型中MERS-COV的保护

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Murine antisera with neutralising activity for the coronavirus causative of Middle East respiratory syndrome (MERS) were induced by immunisation of Balb/c mice with the receptor binding domain (RBD) of the viral Spike protein. The murine antisera induced were fully-neutralising in vitro for two separate clinical strains of the MERS coronavirus (MERS-CoV). To test the neutralising capacity of these antisera in vivo, susceptibility to MERS-CoV was induced in naive recipient Balb/c mice by the administration of an adenovirus vector expressing the human DPP4 receptor (Ad5-hDPP4) for MERS-CoV, prior to the passive transfer of the RBD-specific murine antisera to the transduced mice. Subsequent challenge of the recipient transduced mice by the intra-nasal route with a clinical isolate of the MERS-CoV resulted in a significantly reduced viral load in their lungs, compared with transduced mice receiving a negative control antibody. The murine antisera used were derived from mice which had been primed subcutaneously with a recombinant fusion of RBD with a human IgG Fc tag (RBD-Fc), adsorbed to calcium phosphate microcrystals and then boosted by the oral route with the same fusion protein in reverse micelles. The data gained indicate that this dual-route vaccination with novel formulations of the RBD-Fc, induced systemic and mucosal anti-viral immunity with demonstrated in vitro and in vivo neutralisation capacity for clinical strains of MERS-CoV. Crown Copyright (C) 2019 Published by Elsevier Ltd.
机译:与中和中东呼吸综合征(MERS)的冠状病毒的致病活性的鼠的抗血清通过用病毒刺突蛋白的受体结合结构域(RBD)的Balb / c小鼠的免疫诱导。鼠抗血清诱导在体外完全中和两种单独的MERS冠状病毒(MERS-COV)的临床菌株。为了测试这些抗血清的中和能力在体内,通过施用表达MERS-COV的人DPP4受体(AD5-HDPP4)的腺病毒载体,在幼稚受体BALB / C小鼠中诱导对MERS-COV的易感性。 RBD特异性鼠抗血清的被动转移到转导小鼠。与MERS-COV的临床分离物的鼻内途径通过鼻内途径的随后挑战导致其肺部中的病毒载体显着降低,与接受阴性对照抗体的转导小鼠相比。所用的鼠抗血清源自小鼠,该小鼠皮下映射用RBD的重组融合用L人IgG Fc标签(RBD-Fc),吸附于磷酸钙微晶,然后通过与相同融合蛋白的口腔途径提升胶束。获得的数据表明,该双路由接种的RBD-Fc的新颖的制剂,诱发全身和粘膜的抗病毒免疫在体外和在MERS-CoV病毒株的临床体内中和的能力证实。欧姆维尔有限公司出版的皇冠版权(c)2019

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