Broadly neutralizing antibodies target the coronavirus fusion peptide.

Broadly neutralizing antibodies target the coronavirus fusion peptide.
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DOI:
10.1126/science.abq3773
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发表时间:
2022-08-12
期刊:
Science (New York, N.Y.)
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其他
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未来爆发冠状病毒的可能性突出表明有必要广泛针对这一组病原体。我们使用表位不可知的方法来鉴定六种与所有七种人类感染冠状病毒的刺突蛋白结合的单抗。所有六种抗体都以S2‘裂解位点附近的保守融合肽区为靶点。COV44-62和COV44-79广泛中和甲型和乙型冠状病毒,包括SARS-CoV-2 Omicron亚型BA.2和BA.4/5,尽管效力低于RBD特异性抗体。在COV44-62和COV44-79与SARS-CoV-2融合多肽的晶体结构中,融合多肽表位采用螺旋结构,并在S2‘裂解位点含有精氨酸。COV44-79 SARS-CoV-2在叙利亚仓鼠模型中引起的局限性疾病。这些发现突出了融合肽作为下一代冠状病毒疫苗开发的候选表位。
The potential for future coronavirus outbreaks highlights the need to broadly target this group of pathogens. We use an epitope-agnostic approach to identify six monoclonal antibodies that bind to spike proteins from all seven human-infecting coronaviruses. All six antibodies target the conserved fusion peptide region adjacent to the S2' cleavage site. COV44-62 and COV44-79 broadly neutralize alpha and beta coronaviruses, including SARS-CoV-2 Omicron subvariants BA.2 and BA.4/5, albeit with lower potency than RBD-specific antibodies. In crystal structures of Fabs COV44-62 and COV44-79 with the SARS-CoV-2 fusion peptide, the fusion peptide epitope adopts a helical structure and includes the arginine at the S2' cleavage site. COV44-79 limited disease caused by SARS-CoV-2 in a Syrian hamster model. These findings highlight the fusion peptide as a candidate epitope for next-generation coronavirus vaccine development.
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