title: Evaluation of an inactivated Ross River virus vaccine in active and passive mouse immunization models and establishment of a correlate of protection.
abstract: Ross River Virus has caused reported outbreaks of epidemic polyarthritis, a chronic debilitating disease associated with significant long-term morbidity in Australia and the Pacific region since the 1920s. To address this public health concern, a formalin- and UV-inactivated whole virus vaccine grown in animal protein-free cell culture was developed and tested in preclinical studies to evaluate immunogenicity and efficacy in animal models. After active immunizations, the vaccine dose-dependently induced antibodies and protected adult mice from viremia and interferon α/β receptor knock-out (IFN-α/βR(-/-)) mice from death and disease. In passive transfer studies, administration of human vaccinee sera followed by RRV challenge protected adult mice from viremia and young mice from development of arthritic signs similar to human RRV-induced disease. Based on the good correlation between antibody titers in human sera and protection of animals, a correlate of protection was defined. This is of particular importance for the evaluation of the vaccine because of the comparatively low annual incidence of RRV disease, which renders a classical efficacy trial impractical. Antibody-dependent enhancement of infection, did not occur in mice even at low to undetectable concentrations of vaccine-induced antibodies. Also, RRV vaccine-induced antibodies were partially cross-protective against infection with a related alphavirus, Chikungunya virus, and did not enhance infection. Based on these findings, the inactivated RRV vaccine is expected to be efficacious and protect humans from RRV disease.
authors.affiliation: Baxter Bioscience, Biomedical Research Center, A-2304 Orth/Donau, Austria.
authors.forename: Georg W
authors.initials: GW
authors.lastname: Holzer
authors.forename: Sogue
authors.initials: S
authors.lastname: Coulibaly
authors.forename: Gerald
authors.initials: G
authors.lastname: Aichinger
authors.forename: Helga
authors.initials: H
authors.lastname: Savidis-Dacho
authors.forename: Josef
authors.initials: J
authors.lastname: Mayrhofer
authors.forename: Susanne
authors.initials: S
authors.lastname: Brunner
authors.forename: Karl
authors.initials: K
authors.lastname: Schmid
authors.forename: Otfried
authors.initials: O
authors.lastname: Kistner
authors.forename: John G
authors.initials: JG
authors.lastname: Aaskov
authors.forename: Falko G
authors.initials: FG
authors.lastname: Falkner
authors.forename: Hartmut
authors.initials: H
authors.lastname: Ehrlich
authors.forename: P Noel
authors.initials: PN
authors.lastname: Barrett
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Kreil
mesh_terms: D000293:Adolescent; D000328:Adult; D018354:Alphavirus Infections / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D015415:Biomarkers; D002646:Chikungunya virus / Q000276:immunology; D056738:Cross Protection; D005260:Female; D006801:Humans; D007114:Immunization / Q000379:methods*; D008297:Male; D051379:Mice; D012398:Ross River virus / Q000276:immunology*; D016019:Survival Analysis; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology*; D014766:Viremia / Q000517:prevention & control; D055815:Young Adult
chemical_list: D015415:Biomarkers; D015164:Vaccines, Inactivated; D014765:Viral Vaccines