Synthetic peptide studies on the severe acute respiratory syndrome (SARS) coronavirus spike glycoprotein: Perspective for SARS vaccine development

Synthetic peptide studies on the severe acute respiratory syndrome (SARS) coronavirus spike glycoprotein: Perspective for SARS vaccine development
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DOI:
10.1373/clinchem.2003.029801
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发表时间:
2004-01-01
期刊:
影响因子:
9.3
通讯作者:
Ngai, SM
Ngai, SM
中科院分区:
医学1区
文献类型:
--
作者:
Choy, WY;Lin, SG;Ngai, SM

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背景资料:严重急性呼吸综合征(SARS)的病原冠状病毒(CoV)S(spike)蛋白通过受体结合和病毒粒子与宿主细胞之间的膜融合在介导病毒感染中起核心作用。方法:根据SARS-CoV S蛋白的表面区域设计6个多肽序列,并结合生物信息学和结构分析,对这些多肽序列进行研究。这些合成肽用于免疫兔和猴。第二次免疫后1周收集的抗血清用ELISA分析,并用免疫荧光共聚焦显微镜检测抗SARS-CoV的抗体特异性。我们六种合成肽中的四种(S2、S3、S5和S6)引发SARS-CoV特异性抗体,其中S5(残基788-820)和S6(残基1002-1030)表现出与使用SARS-CoV S蛋白的截短重组蛋白类似物的平行研究中发现的免疫原性应答相似的免疫原性应答。这表明我们的S5和S6肽可能代表了SARS-CoV S蛋白免疫原性区域的两个最小生物活性序列。结论:合成肽可以诱导SARS-CoV特异性抗体。本研究为今后SARS疫苗的合成肽研究提供了新的思路。(C)2004年美国临床化学协会。
Background: The S (spike) protein of the etiologic coronavirus (CoV) agent of severe acute respiratory syndrome (SARS) plays a central role in mediating viral infection via receptor binding and membrane fusion between the virion and the host cell. We focused on using synthetic peptides for developing antibodies against SARS-CoV, which aimed to block viral invasion by eliciting an immune response specific to the native SARS-CoV S protein.Methods: Six peptide sequences corresponding to the surface regions of SARS-CoV S protein were designed and investigated by use of combined bioinformatics and structural analysis. These synthetic peptides were used to immunize both rabbits and monkeys. Antisera collected 1 week after the second immunization were analyzed by ELISA and tested for antibody specificity against SARS-CoV by immunofluorescent confocal microscopy.Results: Four of our six synthetic peptides (S2, S3, S5, and S6) elicited SARS-CoV-specific antibodies, of which S5 (residues 788-820) and S6 (residues 1002-1030) exhibited immunogenic responses similar to those found in a parallel investigation using truncated recombinant protein analogs of the SARS-CoV S protein. This suggested that our S5 and S6 peptides may represent two minimum biologically active sequences of the immunogenic regions of the SARS-CoV S protein.Conclusions: Synthetic peptides can elicit specific antibodies to SARS-CoV. The study provides insights for the future development of SARS vaccine via the synthetic-peptide-based approach. (C) 2004 American Association for Clinical Chemistry.