title: Post-exposure vaccination with MP-12 lacking NSs protects mice against lethal Rift Valley fever virus challenge.
abstract: Rift Valley fever virus (RVFV) causes severe disease in humans and livestock. There are currently no approved antivirals or vaccines for the treatment or prevention of RVF disease in humans. A major virulence factor of RVFV is the NSs protein, which inhibits host transcription including the interferon (IFN)-β gene and promotes the degradation of dsRNA-dependent protein kinase, PKR. We analyzed the efficacy of the live-attenuated MP-12 vaccine strain and MP-12 variants that lack the NSs protein as post-exposure vaccinations. Although parental MP-12 failed to elicit a protective effect in mice challenged with wild-type (wt) RVFV by the intranasal route, significant protection was demonstrated by vaccination with MP-12 strains lacking NSs when they were administered at 20-30 min post-exposure. Viremia and virus replication in liver, spleen and brain were also inhibited by post-exposure vaccination with MP-12 lacking NSs. The protective effect was mostly lost when vaccination was delayed 6 or 24 h after intranasal RVFV challenge. When mice were challenged subcutaneously, efficacy of MP-12 lacking NSs was diminished, most likely due to more rapid dissemination of wt RVFV. Our findings suggest that post-exposure vaccination with MP-12 lacking NSs may be developed as a novel post-exposure treatment to prevent RVF.
authors.affiliation: Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, UT, USA. brian.gowen@usu.edu
authors.forename: Brian B
authors.initials: BB
authors.lastname: Gowen
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Bailey
authors.forename: Dionna
authors.initials: D
authors.lastname: Scharton
authors.forename: Zachery
authors.initials: Z
authors.lastname: Vest
authors.forename: Jonna B
authors.initials: JB
authors.lastname: Westover
authors.forename: Ramona
authors.initials: R
authors.lastname: Skirpstunas
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Ikegami
mesh_terms: D000818:Animals; D005260:Female; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D056990:Post-Exposure Prophylaxis; D012295:Rift Valley Fever / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D012296:Rift Valley fever virus / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D017361:Viral Nonstructural Proteins / Q000235:genetics; D014765:Viral Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014779:Virus Replication
chemical_list: D014613:Vaccines, Attenuated; D017361:Viral Nonstructural Proteins; D014765:Viral Vaccines