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| 1 | A proof of concept for neutralizing antibody-guided vaccine design against SARS-CoV-2显示文摘Mutations and transient conformational movements of the receptor binding domain(RBD)that make neutralizing epitopes momentarily unavailable present immune escape routes for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).To mitigate viral escape,we developed a cocktail of neutralizing antibodies(NAbs)targeting epitopes located on different domains of spike(S)protein.Screening of a library of monoclonal antibodies generated from peripheral blood mononuclear cells of COVID-19 convalescent patients yielded potent NAbs,targeting the N-terminal domain(NTD)and RBD domain of S,effective at n M concentrations.Remarkably,a combination of RBD-targeting NAbs and NTD-binding NAbs,FC05,enhanced the neutralization potency in cell-based assays and an animal model.Results of competitive surface plasmon resonance assays and cryo-electron microscopy(cryo-EM)structures of antigen-binding fragments bound to S unveil determinants of immunogenicity.Combinations of immunogens,identified in the NTD and RBD of S,when immunized in rabbits and macaques,elicited potent protective immune responses against SARS-CoV-2.More importantly,two immunizations of this combination of NTD and RBD immunogens provided complete protection in macaques against a SARS-CoV-2 challenge,without observable antibody-dependent enhancement of infection.These results provide a proof of concept for neutralization-based immunogen design targeting SARS-CoV-2 NTD and RBD. | Li Zhang Lei Cao Xing-Su Gao Bin-Yang Zheng Yong-Qiang Deng Jing-Xin Li Rui Feng Qian Bian Xi-Ling Guo Nan Wang Hong-Ying Qiu Lei Wang Zhen Cui Qing Ye Geng Chen Kui-Kui Lu Yin Chen Yu-Tao Chen Hong-Xing Pan Jiaping Yu Wenrong Yao Bao-Li Zhu Jianping Chen Yong Liu Cheng-Feng Qin Xiangxi Wang Feng-Cai Zhu | 2021 | National Science Review2021，8，8： | 4 |
| 2 | 噬菌体抗体展示技术及其在抗新冠病毒抗体发现中的应用显示文摘噬菌体抗体展示技术是第一个也是目前应用最广泛的体外抗体筛选技术,可用于发现治疗各种疾病的全人源抗体。虽然存在不同的抗体发现方法,但噬菌体抗体展示技术已成为发现和优化靶标特异性单克隆抗体不可或缺的工具。研究人员可通过在丝状噬菌体上创建组合抗体库,从而在几周内获得抗原特异性抗体。在当前冠状病毒病(COVID-19)大流行的情况下,对中和抗体的研究激励着研究人员寻找出抗SARS-CoV-2的候选治疗药物。通过对噬菌体抗体库的筛选,目前已有许多不同的SARS-CoV-2中和抗体被发现。因此,本文综述了噬菌体抗体展示技术的原理,抗体库的构建、分类及淘选流程,并对其优点及局限性进行了讨论。此外,还总结了利用该技术发现抗SARS-CoV-2中和抗体的最新进展。旨为今后该技术在抗体发现中的应用提供理论支持。 | 王加利 和似琦 康子茜 王建勋 | 2022 | 生物技术通报2022，38，5： | 3 |
| 3 | 噬菌体展示技术在现代医药应用的研究进展显示文摘噬菌体展示技术(PDT)是一种高效筛选疾病靶点特异肽的体外筛选技术。PDT不仅能够筛选出疾病相关生物标志物,还可作为药物研究开发的有力工具,目前在疾病的诊断和治疗及药物研究方面具有广泛应用。该研究对PDT的原理及其在疾病诊断、药物研究开发中的应用进行了综述,并探讨了PDT现存的不足和应用前景,以期为PDT在现代医药领域的深入研究提供参考。 | 赵梦瑶 史增芳 宋丽丽 任晓亮 曹颖 | 2023 | 中国医药工业杂志2023，54，1： | 1 |
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