Optimization of antigen dose for a receptor-binding domain-based subunit vaccine against MERS coronavirus.
Optimization of antigen dose for a receptor-binding domain-based subunit vaccine against MERS coronavirus.
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DOI：
10.1080/21645515.2015.1021527
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发表时间：
2015
影响因子：
4.8
通讯作者：
Zhou Y
中科院分区：
文献类型：
--
作者：
Tang J;Zhang N;Tao X;Zhao G;Guo Y;Tseng CT;Jiang S;Du L;Zhou Y
中东呼吸综合征(MERS)是由MERS冠状病毒(MERS-CoV)引起的新发传染病。MERS病例的持续增加已对全球公共卫生构成严重威胁，迫切需要开发安全有效的MERS疫苗。我们先前已经证明，含有MERS冠状病毒受体结合域(RBD)377-588残基的重组蛋白与人Fc融合(S377-588-Fc)，在MF59佐剂存在下可诱导高效的抗MERS-CoV中和抗体。在此，我们以MF59为佐剂，对S377-588-Fc的免疫剂量进行了优化，以期用最少的抗原诱导出较强的免疫应答。结果表明，1μg的S377-588-Fc能诱导小鼠产生较强的体液免疫和细胞免疫应答。特别是，S377-588-Fc在1μg时产生了与5和20μg时相似的针对假型和活MERS冠状病毒的中和抗体反应。这些结果表明，这种基于RBD的MERS亚单位疫苗候选疫苗的剂量低至1μg，足以诱导包括中和抗体在内的针对MERS冠状病毒感染的强大体液和细胞免疫反应，从而为未来临床试验中确定基于RBD的MERS疫苗的最佳剂量提供指导，并为其他亚单位疫苗试验中应用剂量节约策略提供指导。
Middle East respiratory syndrome (MERS) is an emerging infectious disease caused by MERS coronavirus (MERS-CoV). The continuous increase of MERS cases has posed a serious threat to public health worldwide, calling for development of safe and effective MERS vaccines. We have previously shown that a recombinant protein containing residues 377–588 of MERS-CoV receptor-binding domain (RBD) fused with human Fc (S377-588-Fc) induced highly potent anti-MERS-CoV neutralizing antibodies in the presence of MF59 adjuvant. Here we optimized the doses of S377-588-Fc using MF59 as an adjuvant in order to elicit strong immune responses with minimal amount of antigen. Our results showed that S377-588-Fc at 1 μg was able to induce in the immunized mice potent humoral and cellular immune responses. Particularly, S377-588-Fc at 1 μg elicited strong neutralizing antibody responses against both pseudotyped and live MERS-CoV similar to those induced at 5 and 20 μg, respectively. These results suggest that this RBD-based subunit MERS vaccine candidate at the dose as low as one μg is sufficiently potent to induce strong humoral and cellular immune responses, including neutralizing antibodies, against MERS-CoV infection, thus providing guidance for determining the optimal dosage of RBD-based MERS vaccines in the future clinical trials and for applying the dose-sparing strategy in other subunit vaccine trials.