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

Abstract

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.

Serological evidence of virus infection in Eidolon helvum fruit bats: implications for bushmeat consumption in Nigeria

“…On the other hand, a report detected much higher seroprevalence of EBOV antibodies in E. helvum from Cameroon, with 107 out of 817 positive samples (47). Again, it is vital to consider the possibility of crossneutralization, not only with other pathogenic species of ebolaviruses but potentially closely related undiscovered filoviruses, which may not be pathogenic in humans such as the newly discovered Bombali virus in Africa, and shares cross-neutralization against EBOV antibodies (48).…”

A broadly-neutralizing antibody againstEbolavirusglycoprotein that potentiates the breadth and neutralization potency of other antibodies

“…S-FLU viruses could not be successfully pseudotyped with BOMV or TAFV GP. The lack of success of BOMV pseudotyping (due to a difference in the receptor binding site which limits infection of assay target cells) has previously been observed with a lentivirus system and may explain the lack of infection of MDCK SIAT cells in the S-FLU platform with this BOMV GP sequence 30 . Neutralization of wild type BDBV was not tested.…”