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A decoy strategy to activate the immune system
IUBMB Life ( IF 4.6 ) Pub Date : 2021-08-29 , DOI: 10.1002/iub.2548
Manisha S Deshpande 1 , Tanushree Banerjee 1, 2
Affiliation  

An approach comprising a novel fusion protein and inactivated virus, as a more efficacious vaccine against invading viruses is presented, using SARS-CoV-2 as a most prominent example. The fusion protein consists of the Hepatitis B surface antigen (HBsAg) conjugated to the N-terminal helix (NTH) of Angiotensin-Converting Enzyme 2 (ACE2), which is the receptor for SARS-CoV-2. For vaccination, this fusion protein is to be administered together with the whole killed virus. The NTH would bind to the Receptor Binding Domain (RBD) of the Spike protein of the killed virus. Due to HBsAg acting as a decoy, immune responses would be mounted. Neutralizing antibodies (NAbs) pre-existing in people already vaccinated with the recombinant Hepatitis B vaccine, fresh production of NAbs, and NAbs produced by memory B cells would bind to the HBsAg. This would lead to “presentation” of the killed virus to elements of the immune system at close range. Also, there would be enhanced opsonization and effective antigen presentation. This two-component vaccine could be a platform strategy, wherein HBsAg could be linked to the part of the cellular receptor that any new intractable virus binds to, and is administered together with whole inactivated virus. Now, the same fusion protein, administered by itself to persons with infection, would have therapeutic action, yet by harnessing elements of the immune system. NAbs would bind to the fusion protein as above, the NTH of which would bind to the RBDs of the infecting virus, which, in effect would be neutralized.

中文翻译:

激活免疫系统的诱饵策略

提出了一种包含新型融合蛋白和灭活病毒的方法,作为针对入侵病毒的更有效疫苗,以 SARS-CoV-2 作为最突出的例子。融合蛋白由与血管紧张素转换酶 2 (ACE2) 的 N 端螺旋 (NTH) 结合的乙型肝炎表面抗原 (HBsAg) 组成,ACE2 是 SARS-CoV-2 的受体。对于疫苗接种,这种融合蛋白将与整个灭活病毒一起施用。NTH 将与被杀死病毒的 Spike 蛋白的受体结合域 (RBD) 结合。由于 HBsAg 充当诱饵,免疫反应会启动。已经接种重组乙型肝炎疫苗的人体内预先存在的中和抗体 (NAb)、新产生的 NAb 和记忆 B 细胞产生的 NAb 将与 HBsAg 结合。这将导致被杀死的病毒近距离“呈现”给免疫系统的元素。此外,将有增强的调理作用和有效的抗原呈递。这种双组分疫苗可能是一种平台策略,其中 HBsAg 可以与任何新的顽固病毒结合的细胞受体部分相连,并与整个灭活病毒一起给药。现在,同样的融合蛋白,通过自身对感染者的给药,将具有治疗作用,但通过利用免疫系统的元素。NAb 将与上述融合蛋白结合,其 NTH 将与感染病毒的 RBD 结合,这实际上将被中和。将有增强的调理作用和有效的抗原呈递。这种双组分疫苗可能是一种平台策略,其中 HBsAg 可以与任何新的顽固病毒结合的细胞受体部分相连,并与整个灭活病毒一起给药。现在,同样的融合蛋白,通过自身对感染者的给药,将具有治疗作用,但通过利用免疫系统的元素。NAb 将与上述融合蛋白结合,其 NTH 将与感染病毒的 RBD 结合,这实际上将被中和。将有增强的调理作用和有效的抗原呈递。这种双组分疫苗可能是一种平台策略,其中 HBsAg 可以与任何新的顽固病毒结合的细胞受体部分相连,并与整个灭活病毒一起给药。现在,同样的融合蛋白,通过自身对感染者的给药,将具有治疗作用,但通过利用免疫系统的元素。NAb 将与上述融合蛋白结合,其 NTH 将与感染病毒的 RBD 结合,这实际上将被中和。同样的融合蛋白,通过自身对感染者的给药,将具有治疗作用,但通过利用免疫系统的元素。NAb 将与上述融合蛋白结合,其 NTH 将与感染病毒的 RBD 结合,这实际上将被中和。同样的融合蛋白,通过自身对感染者的给药,将具有治疗作用,但通过利用免疫系统的元素。NAb 将与上述融合蛋白结合,其 NTH 将与感染病毒的 RBD 结合,这实际上将被中和。
更新日期:2021-09-27
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