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Prepare for the Future: Dissecting the Spike to Seek Broadly Neutralizing Antibodies and Universal Vaccine for Pandemic Coronaviruses
Frontiers in Molecular Biosciences ( IF 3.9 ) Pub Date : 2020-08-11 , DOI: 10.3389/fmolb.2020.00226
Luca Vangelista , Massimiliano Secchi

Learning from the lengthy fight against HIV-1, influenza, and Ebola virus infection, broadly neutralizing antibodies (bnAbs), directed at conserved regions of surface proteins crucial to virus entry (Env, hemagglutinin, and GP, respectively), are an essential resource for passive as well as active immunization. Rare in their emergence and antigen recognition mode, bnAbs are active toward a large set of different viral strains. Isolation, characterization and production of bnAbs lead to their possible use in passive immunotherapy and form the basis for an educated effort in the development of vaccines for universal coverage. SARS-CoV-2-specific antibodies targeting the spike receptor binding domain (RBD) may lead to antibody dependent enhancement (ADE) of infection, possibly hampering the field of vaccine development. This perspective points to the identification of conserved regions in the spike of SARS-CoV-2, SARS-CoV, and MERS-CoV through investigation, dissection and recombinant production of isolated moieties. These spike moieties should be capable of independent folding and allow the detection as well as the elicitation of bnAbs, thus setting the basis for an effective passive immunotherapy and the development of a universal vaccine against human epidemic coronaviruses (HCoVs). SARS, MERS and, most of all, COVID-19 demonstrate that humanity is the target of HCoV, preparedness for future hits is thus no longer an option.



中文翻译:

为未来做准备:剖析穗以寻求广泛中和的大流行冠状病毒抗体和通用疫苗

通过长期抗击HIV-1,流感和埃博拉病毒感染的经验教训,广泛中和的抗体(bnAb)指向对病毒进入至关重要的表面蛋白的保守区域(分别是Env,血凝素和GP),是必不可少的资源用于被动和主动免疫。bnAb在其出现和抗原识别模式中很少见,对大量不同的病毒株具有活性。bnAbs的分离,鉴定和生产导致它们可能在被动免疫疗法中使用,并为开发针对全民覆盖的疫苗的教育努力奠定了基础。靶向刺突受体结合结构域(RBD)的SARS-CoV-2特异性抗体可能导致感染的抗体依赖性增强(ADE),可能会阻碍疫苗开发领域。该观点指出了通过调查,解剖和重组分离的部分来鉴定SARS-CoV-2,SARS-CoV和MERS-CoV峰中的保守区。这些刺突部分应该能够独立折叠,并能够检测和引发bnAb,从而为有效的被动免疫疗法和开发针对人类流行性冠状病毒(HCoV)的通用疫苗奠定了基础。SARS,MERS和最重要的是COVID-19证明,人类是HCoV的目标,因此不再为未来的流行作好准备。这些刺突部分应该能够独立折叠,并能够检测和引发bnAb,从而为有效的被动免疫疗法和开发针对人类流行性冠状病毒(HCoV)的通用疫苗奠定了基础。SARS,MERS和最重要的是COVID-19证明,人类是HCoV的目标,因此不再为未来的流行作好准备。这些刺突部分应该能够独立折叠,并能够检测和诱导bnAb,从而为有效的被动免疫疗法和开发针对人类流行性冠状病毒(HCoV)的通用疫苗奠定了基础。SARS,MERS和最重要的是COVID-19证明,人类是HCoV的目标,因此不再为未来的流行作好准备。

更新日期:2020-09-01
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