单体和三聚体重组 SARS 冠状病毒刺突蛋白亚单位疫苗候选物的免疫原性和保护效力。
Immunogenicity and protection efficacy of monomeric and trimeric recombinant SARS coronavirus spike protein subunit vaccine candidates.
机构信息
Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
出版信息
Viral Immunol. 2013 Apr;26(2):126-32. doi: 10.1089/vim.2012.0076.
Abstract
Severe acute respiratory syndrome (SARS) is a newly emerging infectious disease, and an effective vaccine is not available. In this study, we compared the immunogenicity and protection efficacy of recombinant proteins corresponding to different domains of the SARS-coronavirus spike protein. Trimeric recombinant proteins were created by fusing the foldon domain derived from T4 bacteriophage to the carboxy-termini of individual domains of the spike protein. While the full-length ectodomain (S) of the spike protein, the full-length ectodomain fused to foldon (S-foldon), the S1 domain (S1), S1-foldon, and the S2 domain(S2) antigens all elicited comparable antibody titers as measured by ELISA, S-foldon induced a significantly higher titer of neutralizing antibody and S2 protein did not elicit virus neutralizing antibodies. When tested in a mouse virus replication model, all the mice vaccinated with the S1, S1-foldon, S, or S-foldon were completely protected.
摘要
严重急性呼吸系统综合症（SARS）是一种新发传染病，目前尚无有效的疫苗。本研究比较了 SARS 冠状病毒刺突蛋白不同结构域的重组蛋白的免疫原性和保护效果。通过将 T4 噬菌体的折叠结构域融合到刺突蛋白的羧基末端，构建了三聚体重组蛋白。全长胞外域（S）、融合折叠结构域的全长胞外域（S-foldon）、S1 结构域（S1）、S1-foldon 和 S2 结构域（S2）抗原均通过 ELISA 检测到相当的抗体滴度，而 S-foldon 诱导的中和抗体滴度显著更高，S2 蛋白不能诱导病毒中和抗体。在小鼠病毒复制模型中检测时，所有用 S1、S1-foldon、S 或 S-foldon 免疫的小鼠均完全得到保护。
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