Evaluation of an inactivated Ross River virus vaccine in active and passive mouse immunization models and establishment of a correlate of protection
Autor(es): Holzer Georg W, Coulibaly Sogue, Aichinger Gerald, Savidis-Dacho Helga, Mayrhofer Josef, Brunner Susanne, Schmid Karl, Kistner Otfried, Aaskov John G, Falkner Falko G, Ehrlich Hartmut, Barrett P Noel, Kreil Thomas R
Resumo: Ross River Virus has caused reported outbreaks of epidemic polyarthritis, a chronic debilitating disease associated with significant long-term morbidity in Australia - the Pacific region since the 1920s. To address this public health concern, a formalin- - UV-inactivated whole virus vaccine grown in animal protein-free cell culture was developed - tested in preclinical studies to evaluate immunogenicity - efficacy in animal models. After active immunizations, the vaccine dose-dependently induced antibodies - protected adult mice from viremia - interferon ?/? receptor knock-out (IFN-?/?R(-/-)) mice from death - disease. In passive transfer studies, administration of human vaccinee sera followed by RRV challenge protected adult mice from viremia - young mice from development of arthritic signs similar to human RRV-induced disease. Based on the good correlation between antibody titers in human sera - 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, - did not enhance infection. Based on these findings, the inactivated RRV vaccine is expected to be efficacious - protect humans from RRV disease.
Palavras-Chave: Vaccines; Ross River virus; Immunization; Passive; Antibody dependent enhancement; IFN?/?-R knock-out mice
Imprenta: Vaccine, v. 29, n. 24, p. 4132-4141, 2011
Identificador do objeto digital: 10.1016/j.vaccine.2011.03.089
Descritores: Chikungunya virus - Cell ; Chikungunya virus - Cytopathology ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Antibodies ; Chikungunya virus - Inflammation ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Vaccine ; Chikungunya virus - Epidemic ; Chikungunya virus - Epidemiology ; Chikungunya virus - Immunology ; Chikungunya virus - Public health
Data de publicação: 2011
