Fig 1.
The live attenuated VSV-EBOV vaccine and EBOV GP functional attributes.
(A) To create an attenuated vaccine for EBOV, the glycoprotein of VSV was replaced with that of EBOV GP. The resulting virus, rVSV-EBOV, forms bullet-shaped particles similar to VSV (Transmission electron microscopy analysis left panels [22,34,35]) rather than the long filaments usually observed for wild-type EBOV. EBOV GP is present on the surface of the chimeric virus in place of VSV G. (B) Recent research has revealed that the EBOV GP (known atomic structure presented in red—PDB-5JQ3 [36]—and cryo-electron tomographic structure of the complete form in outline—EMD-6003 [37]) contains three critical neutralization sites found at the glycan cap, GP1/2 interface, and the stem region, respectively [32,38]. Effective vaccine candidates would be expected to elicit a strong response to these epitopes. The mucin-like domain, which projects from the top of the GP trimer, acts as a shield to prevent immune recognition of neutralization sites [19] and has also been observed to initiate cell activation and the production of inflammatory cytokines in vitro [12]. The transmembrane (TM) domain tethers the GP trimer to the viral membrane and has been implicated in endothelial cell disruption [15]. The adverse effects of the mucin-like domain and the TM domain could be eliminated in future DNA or subunit vaccine lacking these regions.