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Single B cells reveal the antibody responses of rhesus macaques immunized with an inactivated enterovirus D68 vaccine.
Archives of Virology ( IF 2.7 ) Pub Date : 2020-05-28 , DOI: 10.1007/s00705-020-04676-6
Huiwen Zheng 1, 2 , Zening Yang 1, 2 , Bingxiang Li 1 , Heng Li 1, 2 , Lei Guo 1, 2 , Jie Song 1 , Dongpei Hou 1, 2 , Nan Li 1, 2 , Jinxi Yang 1, 2 , Qiongwen Wu 1, 2 , Ming Sun 1 , Longding Liu 1, 2
Affiliation  

Enterovirus D68 (EV-D68) infection may cause severe respiratory system manifestations in pediatric populations. Because of the lack of an effective preventive vaccine or specific therapeutic drug for this infection, the development of EV-D68-specific vaccines and antibodies has become increasingly important. In this study, we prepared an experimental EV-D68 vaccine inactivated by formaldehyde and found that the serum of rhesus macaques immunized with the inactivated EV-D68 vaccine exhibited potent neutralizing activity against EV-D68 virus in vitro. Subsequently, the antibody-mediated immune response of B cells elicited by the inactivated vaccine was evaluated in a rhesus monkey model. The binding activity, in vitro neutralization activity, and sequence properties of 28 paired antibodies from the rhesus macaques' EV-D68-specific single memory B cells were analyzed, and the EV-D68 VP1-specific antibody group was found to be the main constituent in vivo. Intriguingly, we also found a synergistic effect among the E15, E18 and E20 monoclonal antibodies from the rhesus macaques. Furthermore, we demonstrated the protective efficacy of maternal antibodies in suckling C57BL/6 mice. This study provides valuable information for the future development of EV-D68 vaccines.

中文翻译:

单个 B 细胞揭示了用灭活的肠道病毒 D68 疫苗免疫的恒河猴的抗体反应。

肠道病毒 D68 (EV-D68) 感染可能导致儿科人群出现严重的呼吸系统症状。由于缺乏针对这种感染的有效预防疫苗或特异性治疗药物,EV-D68特异性疫苗和抗体的开发变得越来越重要。在这项研究中,我们制备了一种甲醛灭活的实验性 EV-D68 疫苗,发现用灭活的 EV-D68 疫苗免疫的恒河猴血清在体外对 EV-D68 病毒具有有效的中和活性。随后,在恒河猴模型中评估了灭活疫苗引发的 B 细胞的抗体介导免疫反应。恒河猴28对抗体的结合活性、体外中和活性和序列特性 对 EV-D68 特异性单个记忆 B 细胞进行分析,发现 EV-D68 VP1 特异性抗体组是体内的主要成分。有趣的是,我们还发现了来自恒河猴的 E15、E18 和 E20 单克隆抗体之间的协同效应。此外,我们证明了母体抗体对哺乳 C57BL/6 小鼠的保护作用。该研究为EV-D68疫苗的未来开发提供了有价值的信息。
更新日期:2020-05-28
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