title: Vaccination with virus-like particles protects mice from lethal infection of Rift Valley Fever Virus.
abstract: Rift Valley Fever virus (RVFV) regularly accounts for severe and often lethal outbreaks among livestock and humans in Africa. Safe and effective veterinarian and human vaccines are highly needed. We present evidence that administration of RVF virus-like particles (VLPs) induces protective immunity in mice. In an accompanying paper, (Habjan, M., Penski, N., Wagner, V., Spiegel, M., Overby, A.K., Kochs, G., Huiskonen, J., Weber, F., 2009. Efficient production of Rift Valley fever virus-like particles: the antiviral protein MxA can inhibit primary transcription of Bunyaviruses. Virology 385, 400-408) we report the production of these VLPs in mammalian cells. After three subsequent immunizations with 1x10(6) VLPs/dose, high titers of virus-neutralizing antibodies were detected; 11 out of 12 mice were protected from challenge and only 1 out of 12 mice survived infection in the control groups. VLP vaccination efficiently suppressed replication of the challenge virus, whereas in the control animals high RNA levels and increasing antibody titers against the nucleocapsid protein indicated extensive viral replication. Our study demonstrates that the RVF VLPs are highly immunogenic and confer protection against RVFV infection in mice. In the test groups, the vaccinated mice did not exhibit any side effects, and the lack of anti-nucleocapsid protein antibodies serologically distinguished vaccinated animals from experimentally infected animals.
authors.affiliation: Swedish Defence Research Agency, Department of CBRN Defence and Security, SE-901 82 Umeå, Sweden. jonas.naslund@climi.umu.se
authors.forename: Jonas
authors.initials: J
authors.lastname: Näslund
authors.forename: Nina
authors.initials: N
authors.lastname: Lagerqvist
authors.forename: Matthias
authors.initials: M
authors.lastname: Habjan
authors.forename: Ake
authors.initials: A
authors.lastname: Lundkvist
authors.forename: Magnus
authors.initials: M
authors.lastname: Evander
authors.forename: Clas
authors.initials: C
authors.lastname: Ahlm
authors.forename: Friedemann
authors.initials: F
authors.lastname: Weber
authors.forename: Göran
authors.initials: G
authors.lastname: Bucht
mesh_terms: D000818:Animals; D002522:Chlorocebus aethiops; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D009500:Neutralization Tests; D019590:Nucleocapsid Proteins / Q000276:immunology; D012295:Rift Valley Fever / Q000276:immunology* / Q000517:prevention & control; D012296:Rift Valley fever virus / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D016019:Survival Analysis; D014611:Vaccination; D014709:Vero Cells / Q000821:virology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology*; D014771:Virion / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D019590:Nucleocapsid Proteins; D014765:Viral Vaccines