美国国立卫生研究院
研究人员使用了一种表位诊断的方法来确定六种单克隆抗体，它们与所有七种人类感染的冠状病毒突刺蛋白结合。所有这六种抗体都针对与S2′切割位点相邻的保守融合肽区域。COV44-62和COV44-79广泛中和α-和β-冠状病毒，包括严重急性呼吸道综合征冠状病毒2（SARS-CoV-2）Omicron亚变体BA.2和BA.4/5，尽管其效力低于受体结合域特异性抗体。在COV44-62和COV44-79与SARS-CoV-2融合肽的抗原结合片段的晶体结构中，融合肽表位采用螺旋结构，包括S2′切割位点的精氨酸残基。COV44-79限制了叙利亚仓鼠模型中由SARS-CoV-2引起的疾病。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。
据悉，未来冠状病毒爆发的可能性突出了广泛靶向这类病原体的必要性。
附：英文原文
Title: Broadly neutralizing antibodies target the coronavirus fusion peptide
Author: Cherrelle Dacon, Courtney Tucker, Linghang Peng, Chang-Chun D. Lee, Ting-Hui Lin, Meng Yuan, Yu Cong, Lingshu Wang, Lauren Purser, Jazmean K. Williams, Chul-Woo Pyo, Ivan Kosik, Zhe Hu, Ming Zhao, Divya Mohan, Andrew J. R. Cooper, Mary Peterson, Jeff Skinner, Saurabh Dixit, Erin Kollins, Louis Huzella, Donna Perry, Russell Byrum, Sanae Lembirik, David Drawbaugh, Brett Eaton, Yi Zhang, Eun Sung Yang, Man Chen, Kwanyee Leung, Rona S. Weinberg, Amarendra Pegu, Daniel E. Geraghty, Edgar Davidson, Iyadh Douagi, Susan Moir, Jonathan W. Yewdell, Connie Schmaljohn, Peter D. Crompton, Michael R. Holbrook, David Nemazee, John R. Mascola, Ian A. Wilson, Joshua Tan
Issue&Volume: 2022-07-12
Abstract: The potential for future coronavirus outbreaks highlights the need to broadly target this group of pathogens. We used 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 betacoronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants BA.2 and BA.4/5, albeit with lower potency than receptor binding domain–specific antibodies. In crystal structures of COV44-62 and COV44-79 antigen-binding fragments with the SARS-CoV-2 fusion peptide, the fusion peptide epitope adopts a helical structure and includes the arginine residue 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.
DOI: abq3773
Source: https://www.science.org/doi/10.1126/science.abq3773