Vesicular stomatitis virus-based Ebola vaccines with improved cross-protective efficacy

Andrea Marzi, Hideki Ebihara, Julie Callison, Allison Groseth, Kinola J. Williams, Thomas W. Geisbert, Heinz Feldmann

Research output: Contribution to journalArticlepeer-review

100 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)S1066-S1074
JournalJournal of Infectious Diseases
Volume204
Issue numberSUPPL. 3
DOIs
StatePublished - Nov 1 2011

ASJC Scopus subject areas

  • General Medicine

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