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基于刺突蛋白的 MERS-CoV 候选 DNA 疫苗的免疫原性。

Immunogenicity of Candidate MERS-CoV DNA Vaccines Based on the Spike Protein.

机构信息

Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.

Biotechnology Research Laboratories, Gastroenterology Surgery Center, Mansoura University, Mansoura, Egypt.

出版信息

Sci Rep. 2017 Mar 23;7:44875. doi: 10.1038/srep44875.

Abstract

MERS-coronavirus is a novel zoonotic pathogen which spread rapidly to >25 countries since 2012. Its apparent endemicity and the wide spread of its reservoir host (dromedary camels) in the Arabian Peninsula highlight the ongoing public health threat of this virus. Therefore, development of effective prophylactic vaccine needs to be urgently explored given that there are no approved prophylactics or therapeutics for humans or animals to date. Different vaccine candidates have been investigated but serious safety concerns remain over protein or full-length spike (S) protein-based vaccines. Here, we investigated the immunogenicity of naked DNA vaccines expressing different fragments of MERS-CoV S protein in mice. We found that plasmids expressing full-length (pS) or S1-subunit (pS1) could induce significant levels of S1-specific antibodies (Abs) but with distinct IgG isotype patterns. Specifically, pS1 immunization elicited a balanced Th1/Th2 response and generally higher levels of all IgG isotypes compared to pS vaccination. Interestingly, only mice immunized with pS1 demonstrated significant S1-specific cellular immune response. Importantly, both constructs induced cross-neutralizing Abs against multiple strains of human and camel origins. These results indicate that vaccines expressing S1-subunit of the MERS-CoV S protein could represent a potential vaccine candidate without the possible safety concerns associated with full-length protein-based vaccines.

摘要

MERS 冠状病毒是一种新型人畜共患病病原体,自 2012 年以来迅速传播到 25 个以上的国家。其明显的地方性和在阿拉伯半岛广泛传播的储主(单峰骆驼)突出了该病毒对持续存在的公共卫生威胁。因此,鉴于目前尚无针对人类或动物的批准预防药物或治疗药物,迫切需要探索有效的预防性疫苗。已经研究了不同的疫苗候选物,但基于蛋白质或全长刺突(S)蛋白的疫苗仍然存在严重的安全问题。在这里,我们研究了在小鼠中表达不同片段的 MERS-CoV S 蛋白的裸露 DNA 疫苗的免疫原性。我们发现,表达全长(pS)或 S1 亚单位(pS1)的质粒可以诱导出显著水平的 S1 特异性抗体(Abs),但 IgG 同种型模式不同。具体而言,pS1 免疫接种可诱导平衡的 Th1/Th2 反应,并且与 pS 疫苗相比,通常可诱导更高水平的所有 IgG 同种型。有趣的是,只有用 pS1 免疫的小鼠显示出明显的 S1 特异性细胞免疫反应。重要的是,这两种构建体均诱导针对来自人和骆驼的多种株的交叉中和抗体。这些结果表明,表达 MERS-CoV S 蛋白的 S1 亚单位的疫苗可能是一种潜在的疫苗候选物,而不会出现与全长蛋白基疫苗相关的可能安全问题。

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