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.

• Authors: Andrea Marzi, Hideki Ebihara, Julie Callison, Allison Groseth, Kinola J Williams, Thomas W Geisbert, Heinz Feldmann
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 204 Suppl 3 Pg. S1066-74 (Nov 2011) ISSN: 1537-6613 [Electronic] United States
• PMID: 21987743 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Viral
• Ebola Vaccines
• Vaccines, Attenuated
• Vaccines, Synthetic

Topics

• Animals
• Antigens, Viral (immunology)
• Chlorocebus aethiops
• Ebola Vaccines (administration & dosage, immunology)
• Ebolavirus (classification, immunology)
• Female
• Guinea Pigs
• HEK293 Cells
• Hemorrhagic Fever, Ebola (prevention & control, virology)
• Humans
• Immunization Schedule
• Mice
• Mice, Inbred BALB C
• Plasmids
• Vaccines, Attenuated
• Vaccines, Synthetic
• Vero Cells
• Vesiculovirus