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RSV疫苗及药物研发整体解决方案

RSV疫苗及药物研发整体解决方案
背景
人类呼吸道合胞病毒(Human Respiratory Syncytial Virus, HRSV)为肺炎病毒科,正肺病毒属的RNA病毒,具有季节性流行病传播模式,多发于婴儿、患有慢性心脏或肺部疾病的成人、免疫系统较弱的人以及65岁以上的老年人,临床症状包括咳嗽、喘息,极少部分进一步加重出现呼吸急促和喂养困难等,严重者可发展为呼吸衰竭甚至死亡。

HRSV基因组全长约15.2kb,编码11个蛋白质。其中黏附蛋白 (Glycoproteins Protein,G) 、融合蛋白(Fusion Protein,F) 是HRSV膜表面主要糖蛋白,为病毒重要的抗原蛋白,是刺激机体产生中和抗体的主要病毒抗原。HRSV只有一个血清型,分为A、B两个亚型,国际上依据G基因第二高变区的基因变异将HRSV划分为不同基因型,已鉴定出45个基因型。目前A亚型的ON1基因型和B亚型的BA9基因型是全球流行的优势基因型,也是我国近年流行的主要基因型。

RSV疫苗及药物研发整体解决方案
RSV F 蛋白介导的融合过程(10.1038/s41579-019-0149-x)

RSV F 蛋白介导的融合过程(10.1038/s41579-019-0149-x)

与大多数病毒融合蛋白相似,RSV的F蛋白以跨膜三聚体形式存在,三个相同的单体通过部分相互缠绕而形成,具有融合前pre-F和融合后post-F两种构象。Pre-F构象的三聚体RSV F蛋白通过C末端跨膜结构域锚定在病毒包膜上,其顶端存在被高中和活性抗体靶向的表位,F蛋白重排(在病毒膜上自发重排,或者与宿主细胞膜形成融合孔后重排)成Post-F构象之后,表位消失。因此,保留顶端中和敏感表位的Pre-F构象蛋白是RSV疫苗开发的首选抗原。
RSV疫苗研究的分水岭

2013年前:针对融合后F蛋白(Post-F)设计研发

2013年后:针对融合前F蛋白(Pre-F)设计研发

这一变化主要源于:
MCLELLAN 等对F蛋白进行优化改造,获得了稳定的,融合前F蛋白(Pre-F),并发现了新的中和抗体表位ø,Pre-F特有的抗原表位ø产生中和抗体的活性最强,较针对其他表位产生的抗体中和活性高几十倍。

DOI: 10.1126/science.1234914
RSV-F蛋白抗原表位及抗体结合情况

RSV疫苗研究的分水岭
最新研究再次证实,RSV Pre-F蛋白相比Post-F蛋白可诱导更高滴度的中和抗体且能激活更多的记忆B细胞,其中特异性结合pre-F 顶端区域的中和抗体,具有更高效的中和活性。

DOI: 10.1126/scitranslmed.ade9984
DOI: 10.1126/scitranslmed.ade0424

RSV F蛋白构象对疫苗开发和评估过程至关重要,Pre-F形式可以诱导更有效的中和抗体,而Post-F可以用作筛选Pre-F特异性抗体时的对照。ACROBiosystems百普赛斯为支持RSV相关研究及疫苗研发,推出RSV疫苗研发整体解决方案!
RSV疫苗研发整体解决方案

*点击查看RSV相关产品

产品名称 分子 货号 产品描述
抗原 Glycoprotein G / G RSG-V5221 HRSV (A) Glycoprotein G Protein, His Tag
Post-Fusion glycoprotein F0 RSF-V52H6 HRSV (A) Post-fusion glycoprotein F0, His Tag (MALS verified)
Post-Fusion glycoprotein F0 RSF-V52H9 HRSV (B) Post-fusion glycoprotein F0, His Tag (MALS verified)
Pre-Fusion glycoprotein F0 RSF-V52H3 FITC-Labeled Human respiratory syncytial virus A (strain A2) Pre-F0 Protein, His Tag
Pre-Fusion glycoprotein F0 RSF-V52H7 HRSV (A) Pre-fusion glycoprotein F0, His Tag (MALS verified)
Pre-Fusion glycoprotein F0 RSF-V52H8 HRSV (B) Pre-fusion glycoprotein F0, His Tag (MALS verified)
Pre-Fusion glycoprotein F0 RSF-V82E7 Biotinylated Human respiratory syncytial virus A (strain A2) Pre-F0 Protein, His,Avitag™(MALS verified)
抗体 RSV-post-F0 RSV-M662 Monoclonal Anti-RSV-post-F0 specific Antibody, Human IgG1 (1A2D9D8)
RSV-post-F0 RSV-Y180 Monoclonal Anti-RSV-post-F0 specific Antibody, Mouse IgG1 (1A2D9D8)
RSV-Pre-F0 RS0-S286 Monoclonal Anti-RSV-Pre-F0 specific Antibody, Human IgG1 (12C6)
RSV-Pre-F0 RS0-Y132 Monoclonal Anti-RSV-Pre-F0 specific Antibody, Mouse IgG1 (12C6)
试剂盒 Post-Fusion glycoprotein F0 RAS-A169 HRSV Post-Fusion glycoprotein F0 Specific ELISA Kit(For Vaccine Development)
Post-Fusion glycoprotein F0 RAS-T168 Mouse Anti-RSV-F0 Antibody IgG Titer ELISA Assay Kit (Post-Fusion glycoprotein F0)
Pre-Fusion glycoprotein F0 RAS-A159 HRSV Pre-Fusion glycoprotein F0 Specific ELISA Kit
Pre-Fusion glycoprotein F0 RAS-A176 HRSV Pre-Fusion glycoprotein F0(site Ø) Specific ELISA Kit
Pre-Fusion glycoprotein F0 RAS-A177 HRSV Pre-Fusion glycoprotein F0(site Ø&V) Specific ELISA Kit
Pre-Fusion glycoprotein F0 RAS-A178 HRSV Pre-Fusion glycoprotein F0(site V) Specific ELISA Kit (For Vaccine Development)
Pre-Fusion glycoprotein F0 RAS-A182 HRSV Fusion glycoprotein F0(site IV) Specific ELISA Kit
Pre-Fusion glycoprotein F0 RAS-A183 HRSV Fusion glycoprotein F0(site I) Specific ELISA Kit
Pre-Fusion glycoprotein F0 RAS-T172 Cotton Rat Anti-RSV-F0 Antibody IgG Titer ELISA Assay Kit (Pre-Fusion glycoprotein F0)
Pre-Fusion glycoprotein F0 RAS-T174 Mouse Anti-RSV-F0 Antibody IgG Titer ELISA Assay Kit (Pre-Fusion glycoprotein F0)
Pre-Fusion glycoprotein F0 RAS-T175 Human Anti-RSV-F0 Antibody IgG Titer ELISA Assay Kit (Pre-Fusion glycoprotein F0)
RSV-F0 RAS-P166 Anti-RSV-Pre-F0 specific Antibody IgG Pair
RSV-F0 RAS-T162 Monkey Anti-RSV-F0 Antibody IgG Titer ELISA Assay Kit (Pre-Fusion glycoprotein F0)
产品优势

特殊设计的天然构象:经特殊设计具有天然三聚体构象的融合前Pre-F蛋白、融合后Post-F蛋白以及G蛋白。

产品类型丰富:覆盖正确构象的RSV Pre-F、Post-F和G蛋白、RSV-F0广谱抗体和Pre-F0特异性抗体、Pre-F0抗原及抗体检测试剂盒;

高纯度:经SDS-PAGE及SEC-MALS验证纯度>90%。

高活性:经ELISA验证Pre-F及Post-F蛋白与其特异性抗体结合能力强。

高免疫原性:天然构象RSV-F和G蛋白可诱导产生更高的抗体滴度。

验证数据
天然三聚体构象Pre-F蛋白验证数据
经SEC-MALS验证Pre-F三聚体蛋白纯度>90%
天然三聚体构象Pre-F蛋白验证数据

The purity of HRSV (A) Fusion glycoprotein F0, His Tag (Cat. No. RSF-V52H7) is more than 90% and the molecular weight of this protein is around 175-200 kDa verified by SEC-MALS.

经ELISA验证,Pre-F三聚体蛋白与Pre-F特异性抗体(D25)结合线性范围为0.2-1 ng/mL
天然三聚体构象Pre-F蛋白验证数据

Immobilized HRSV (A) Fusion glycoprotein F0, His Tag (Cat. No. RSF-V52H7) at 2 μg/mL (100 μL/well) can bind Anti-Fusion glycoprotein F0 Antibody, Human IgG1 (D25) with a linear range of 0.2-1 ng/mL (QC tested).

Pre-F特异性抗体产品验证数据
经ELISA验证,Pre-F特异性抗体12C6可特异性识别Pre-F三聚体,与Post-F三聚体不结合
Pre-F特异性抗体产品验证数据

Immobilized HRSV (A) Pre-fusion glycoprotein F0, His Tag (Cat. No. RSF-V52H7) at 1 μg/mL (100 μL/well) can bind Monoclonal Anti-RSV-Pre-F0 specific Antibody, Human IgG1 (12C6) (Cat. No. RS0-S286) with a linear range of 0.2-2 ng/mL. HRSV (A) Post-fusion glycoprotein F0, His Tag (Cat. No. RSF-V52H6) is verified not recoginized by Monoclonal Anti-RSV-Pre-F0 specific Antibody, Human IgG1 (12C6) (Cat. No. RS0-S286) in low concentration (QC tested).

ELISA检测试剂盒
ELISA检测试剂盒

Detection of Pre-Fusion glycoprotein F0 (RSV) by sandwich-ELISA Assay.Immobilized Anti-Pre-Fusion glycoprotein F0 (RSV) Antibody can bind Pre-Fusion glycoprotein F0 (RSV). Detection was performed using HRP-Anti-Pre-Fusion glycoprotein F0 (RSV) Antibody with sensitivity of 3.1 ng/mL (QC tested).

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