Cross-Neutralisation of Novel Bombali Virus by Ebola Virus Antibodies and Convalescent Plasma Using an Optimised Pseudotype-Based Neutralisation Assay.

Cross-Neutralisation of Novel Bombali Virus by Ebola Virus Antibodies and Convalescent Plasma Using an Optimised Pseudotype-Based Neutralisation Assay.
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DOI:
10.3390/tropicalmed6030155
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发表时间:
2021-08-25
影响因子:
2.9
通讯作者:
Wright E
Wright E
中科院分区:
医学3区
文献类型:
--
作者:
Bentley EM;Richardson S;Derveni M;Rijal P;Townsend AR;Heeney JL;Mattiuzzo G;Wright E

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埃博拉病毒继续构成重大疫情威胁,虽然埃博拉病毒(EBOV)特异性疫苗和抗病毒药已获得许可,但仍在继续努力开发提供广泛物种交叉保护的候选药物。使用假型病毒代替活病毒被认为是一种替代的、更安全的、高通量的平台,以评估抗埃博拉病毒抗体的发展,但它需要优化。在此,我们已经证明靶细胞系会影响中和试验结果,并且不能纯粹基于允许性进行选择。在扩展平台以整合每个埃博拉病毒种属的包膜糖蛋白,从而全面评估交叉中和的过程中,我们发现最近发现的Bombali病毒在受体结合结构域中具有点突变,该点突变阻止进入仓鼠细胞系,并且重要的是,表明该病毒可以被EBOV抗体和恢复期血浆交叉中和。
Ebolaviruses continue to pose a significant outbreak threat, and while Ebola virus (EBOV)-specific vaccines and antivirals have been licensed, efforts to develop candidates offering broad species cross-protection are continuing. The use of pseudotyped virus in place of live virus is recognised as an alternative, safer, high-throughput platform to evaluate anti-ebolavirus antibodies towards their development, yet it requires optimisation. Here, we have shown that the target cell line impacts neutralisation assay results and cannot be selected purely based on permissiveness. In expanding the platform to incorporate each of the ebolavirus species envelope glycoprotein, allowing a comprehensive assessment of cross-neutralisation, we found that the recently discovered Bombali virus has a point mutation in the receptor-binding domain which prevents entry into a hamster cell line and, importantly, shows that this virus can be cross-neutralised by EBOV antibodies and convalescent plasma.
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