Figure 1.

Logical representation of the vesicular stomatitis virus (VSV) genome structure. The natural VSV genome (a) is composed of five open reading frames bounded by a 3′ leader sequence (Le) and a 5′ trailer region (Tr). Sequences coding for foreign antigens can be inserted in 3′ of the nucleoprotein (N) gene and between the glycoprotein (G) and large polymerase protein (L) genes. These locations are indicated by broken lines in (a). The Ebola vaccine was designed by replacing the VSV G protein with the Ebola G protein, leading to a replicating pseudotyped vector (b). Similarly, a severe acute respiratory syndrome (SARS) vaccine was designed by replacing the VSV G protein with the SARS spike (S) protein (c). The avian influenza vaccine relies on the insertion of a sequence coding for the H5 antigen immediately next to the leader sequence (d). Interestingly, the booster vaccine carries a different variant of the VSV G protein to escape the anti-VSV immune response acquired during the primary immunization. The tuberculosis vaccine relies on the insertion of an antigen between G and L (e). The Yersinia pestis vaccine is structurally comparable to the avian influenza vaccine (f). Finally, the anti-inflammatory oncolytic VSV has a large insert between G and L. The insert includes an anti-inflammatory glycoprotein (EHV1G) and a reporter gene (Luc) separated by an internal ribosome entry site (IRES) (g). These logical maps were generated using GenoCAD [11].