title: Kunjin virus replicon-based vaccines expressing Ebola virus glycoprotein GP protect the guinea pig against lethal Ebola virus infection.
abstract: Pre- or postexposure treatments against the filoviral hemorrhagic fevers are currently not available for human use. We evaluated, in a guinea pig model, the immunogenic potential of Kunjin virus (KUN)-derived replicons as a vaccine candidate against Ebola virus (EBOV). Virus like particles (VLPs) containing KUN replicons expressing EBOV wild-type glycoprotein GP, membrane anchor-truncated GP (GP/Ctr), and mutated GP (D637L) with enhanced shedding capacity were generated and assayed for their protective efficacy. Immunization with KUN VLPs expressing full-length wild-type and D637L-mutated GPs but not membrane anchor-truncated GP induced dose-dependent protection against a challenge of a lethal dose of recombinant guinea pig-adapted EBOV. The surviving animals showed complete clearance of the virus. Our results demonstrate the potential for KUN replicon vectors as vaccine candidates against EBOV infection.
authors: Filovirus Laboratory, INSERM U758, Human Virology Department, Claude Bernard University Lyon-1, Université de Lyon, Ecole Normale Supérieure de Lyon, Lyon, France.
authors: O
authors: O
authors: Reynard
authors: V
authors: V
authors: Mokhonov
authors: E
authors: E
authors: Mokhonova
authors: J
authors: J
authors: Leung
authors: A
authors: A
authors: Page
authors: M
authors: M
authors: Mateo
authors: O
authors: O
authors: Pyankova
authors: M C
authors: MC
authors: Georges-Courbot
authors: H
authors: H
authors: Raoul
authors: A A
authors: AA
authors: Khromykh
authors: V E
authors: VE
authors: Volchkov
mesh_terms: D000818:Animals; D004306:Dose-Response Relationship, Immunologic; D046129:Ebola Vaccines / Q000276:immunology*; D015967:Gene Expression Regulation, Viral; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology; D006168:Guinea Pigs; D019142:Hemorrhagic Fever, Ebola / Q000517:prevention & control*; D009154:Mutation; D013997:Time Factors; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; D014902:West Nile virus
chemical_list: D046129:Ebola Vaccines; D006023:Glycoproteins; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic