title: 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: Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institute of Health, Hamilton, Montana 59840, USA.
authors: Andrea
authors: A
authors: Marzi
authors: Hideki
authors: H
authors: Ebihara
authors: Julie
authors: J
authors: Callison
authors: Allison
authors: A
authors: Groseth
authors: Kinola J
authors: KJ
authors: Williams
authors: Thomas W
authors: TW
authors: Geisbert
authors: Heinz
authors: H
authors: Feldmann
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D002522:Chlorocebus aethiops; D046129:Ebola Vaccines / Q000008:administration & dosage / Q000276:immunology*; D029043:Ebolavirus / Q000145:classification / Q000276:immunology*; D005260:Female; D006168:Guinea Pigs; D057809:HEK293 Cells; D019142:Hemorrhagic Fever, Ebola / Q000517:prevention & control* / Q000821:virology; D006801:Humans; D007115:Immunization Schedule; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; D014709:Vero Cells; D018116:Vesiculovirus
chemical_list: D000956:Antigens, Viral; D046129:Ebola Vaccines; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic