Vesicular Stomatitis Virus–Based Ebola Vaccines With Improved Cross-Protective Efficacy

Abstract

For Ebola virus (EBOV), 4 different species are known: Zaire, Sudan, Côte d'Ivoire, and Reston ebolavirus. The newly discovered Bundibugyo ebolavirus has been proposed as a 5th species. So far, no cross-neutralization among EBOV species has been described, aggravating progress toward cross-species protective vaccines. With the use of recombinant vesicular stomatitis virus (rVSV)-based vaccines, guinea pigs could be protected against Zaire ebolavirus (ZEBOV) infection only when immunized with a vector expressing the homologous, but not a heterologous, EBOV glycoprotein (GP). However, infection of guinea pigs with nonadapted wild-type strains of the different species resulted in full protection of all animals against subsequent challenge with guinea pig-adapted ZEBOV, showing that cross-species protection is possible. New vectors were generated that contain EBOV viral protein 40 (VP40) or EBOV nucleoprotein (NP) as a second antigen expressed by the same rVSV vector that encodes the heterologous GP. After applying a 2-dose immunization approach, we observed an improved cross-protection rate, with 5 of 6 guinea pigs surviving the lethal ZEBOV challenge if vaccinated with rVSV-expressing SEBOV-GP and -VP40. Our data demonstrate that cross-protection between the EBOV species can be achieved, although EBOV-GP alone cannot induce the required immune response.

Vesicular Stomatitis Virus Pseudotyped with Ebola Virus Glycoprotein Serves as a Protective, Noninfectious Vaccine against Ebola Virus Challenge in Mice

“…These results indicate that VSVΔG pseudovirion-based vaccines against EBOV elicit protective immune responses that can be independent of the production of antibodies that neutralize viral particles in cell culture assays. Consistent with our findings, protection conferred by other EBOV vaccines does not always correlate with the production of neutralizing antibodies (12,13,39,40).…”

Antibodies are necessary for rVSV/ZEBOV-GP–mediated protection against lethal Ebola virus challenge in nonhuman primates

“…Viral loads were determined using qRT-PCR and titration assays as described previously (34). Blood cell count from whole EDTA blood was determined with the HemaVet 950FS+ laser-based hematology analyzer (Drew Scientific).…”

“…Antibody titers directed against ZEBOV-GP or ZEBOV-VP40 were measured by ELISA using plates coated with recombinant proteins. Neutralizing antibody titers were determined by performing focus reduction neutralization titration assays as described previously (34). For detailed information, see SI Materials and Methods.…”

The vesicular stomatitis virus-based Ebola virus vaccine: From concept to clinical trials

“…In contrast, there was no cross-species protection in guinea pigs immunized with VSV-based vaccines bearing the GPs of Bundibugyo virus (BDBV), TAFV, RESTV, or SUDV when challenged with guinea pig-adapted EBOV. 22 However, vaccination of cynomolgus macaques with VSV-EBOV resulted in partial protection against BDBV infection 23 and vaccination with VSV-EBOV in a prime-boost regimen resulted in complete protection against BDBV. 24 Taken together, there is limited interspecies cross-protection afforded by the VSV-EBOV vaccine; efficient cross-species protection will most likely require different approaches such as blending of several monovalent VSV vaccine vectors expressing the glycoproteins of different Ebolavirus species, expression of additional viral proteins from a multivalent VSV-EBOV vector, or expression of different ebolavirus GPs from a multivalent VSV vector.…”

“…24 Taken together, there is limited interspecies cross-protection afforded by the VSV-EBOV vaccine; efficient cross-species protection will most likely require different approaches such as blending of several monovalent VSV vaccine vectors expressing the glycoproteins of different Ebolavirus species, expression of additional viral proteins from a multivalent VSV-EBOV vector, or expression of different ebolavirus GPs from a multivalent VSV vector. 22 , 25 , 26 …”