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A double-inactivated whole virus candidate SARS coronavirus vaccine stimulates neutralising and protective antibody responses

机译:双重灭活的全病毒候选SARS冠状病毒疫苗可刺激中和和保护性抗体反应

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摘要

A double-inactivated, candidate whole virus vaccine against severe acute respiratory syndrome associated coronavirus (SARS-CoV) was developed and manufactured at large scale using fermenter cultures of serum protein free Vero cells. A two step inactivation procedure involving sequential formaldehyde and U.V. inactivation was utilised in order to ensure an extremely high safety margin with respect to residual infectivity. The immunogenicity of this double-inactivated vaccine was characterised in the mouse model. Mice that were immunised twice with the candidate SARS-CoV vaccine developed high antibody titres against the SARS-CoV spike protein and high levels of neutralising antibodies. The use of the adjuvant Al(OH)3 had only a minor effect on the immunogenicity of the vaccine. In addition, cell mediated immunity as measured by interferon-gamma and interleukin-4 stimulation, was elicited by vaccination. Moreover, the vaccine confers protective immunity as demonstrated by prevention of SARS-CoV replication in the respiratory tract of mice after intranasal challenge with SARS-CoV. Protection of mice was correlated to antibody titre against the SARS-CoV S protein and neutralising antibody titre.
机译:针对严重急性呼吸系统综合症冠状病毒(SARS-CoV)的双灭活候选全病毒疫苗已开发出来,并使用无血清蛋白Vero细胞的发酵罐进行大规模培养。分两步进行的灭活步骤,涉及顺序甲醛和紫外线。为了确保在残留传染性方面的极高的安全裕度,使用了灭活。在小鼠模型中表征了这种双重灭活疫苗的免疫原性。用候选SARS-CoV疫苗免疫两次的小鼠对SARS-CoV刺突蛋白的抗体效价高,中和抗体水平高。佐剂Al(OH)3的使用对疫苗的免疫原性仅有很小的影响。另外,通过疫苗接种引起了如干扰素-γ和白介素-4刺激所测量的细胞介导的免疫。此外,该疫苗具有保护性免疫功能,如通过鼻内用SARS-CoV攻击后防止SARS-CoV在小鼠呼吸道中复制所证明的那样。小鼠的保护与针对SARS-CoV S蛋白的抗体滴度和中和抗体滴度相关。

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