Zeng Fanya, Chow Ken Yan Ching, Hon Chung Chau, Law Ka Man, Yip Chi Wai, Chan Kwok Hung, Peiris Joseph S Malik, Leung Frederick Chi Ching
Department of Zoology, The University of Hong Kong, Pokfulam Rd, Hong Kong, SAR, China.
Biochem Biophys Res Commun. 2004 Mar 19;315(4):1134-9. doi: 10.1016/j.bbrc.2004.01.166.
The immunological characteristics of SARS-CoV spike protein were investigated by administering mice with plasmids encoding various S gene fragments. We showed that the secreting forms of S1, S2 subunits and the N-terminus of S1 subunit (residues 18-495) were capable of eliciting SARS-CoV specific antibodies and the region immediate to N-terminus of matured S1 protein contained an important immunogenic determinant for elicitation of SARS-CoV specific antibodies. In addition, mice immunized with plasmids encoding S1 fragment developed a Th1-mediated antibody isotype switching. Another interesting finding was that mouse antibodies elicited separately by plasmids encoding S1 and S2 subunits cooperatively neutralized SARS-CoV but neither the S1 nor S2 specific antibodies did, suggesting the possible role of both S1 and S2 subunits in host cell docking and entry. These results provide insights into understanding the immunological characteristics of spike protein and the development of subunit vaccines against SARS-CoV.
通过给小鼠注射编码各种S基因片段的质粒,研究了SARS-CoV刺突蛋白的免疫特性。我们发现,S1、S2亚基以及S1亚基的N端(第18-495位氨基酸)的分泌形式能够引发SARS-CoV特异性抗体,并且成熟S1蛋白紧邻N端的区域包含一个引发SARS-CoV特异性抗体的重要免疫原性决定簇。此外,用编码S1片段的质粒免疫的小鼠发生了Th1介导的抗体亚型转换。另一个有趣的发现是,分别由编码S1和S2亚基的质粒引发的小鼠抗体协同中和SARS-CoV,但单独的S1或S2特异性抗体则不能,这表明S1和S2亚基在宿主细胞对接和进入过程中可能发挥作用。这些结果为理解刺突蛋白的免疫特性以及开发针对SARS-CoV的亚单位疫苗提供了思路。