Post-exposure vaccination with MP-12 lacking NSs protects mice against lethal Rift Valley fever virus challenge

Brian B. Gowen, Kevin W. Bailey, Dionna Scharton, Zachery Vest, Jonna B. Westover, Ramona Skirpstunas, Tetsuro Ikegami

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)135-143
Number of pages9
JournalAntiviral Research
Volume98
Issue number2
DOIs
StatePublished - 2013

Fingerprint

Rift Valley fever virus
Vaccination
Vaccines
eIF-2 Kinase
Viremia
Livestock
Virulence Factors
Virus Replication
Interferons
Antiviral Agents
Proteins
Spleen
12-nitroxide stearate
Liver
Brain
Therapeutics
Genes

Keywords

  • Phlebovirus
  • Post-exposure vaccination
  • Rift Valley fever virus
  • Treatment
  • Viral hemorrhagic fever

ASJC Scopus subject areas

  • Virology
  • Pharmacology

Cite this

Post-exposure vaccination with MP-12 lacking NSs protects mice against lethal Rift Valley fever virus challenge. / Gowen, Brian B.; Bailey, Kevin W.; Scharton, Dionna; Vest, Zachery; Westover, Jonna B.; Skirpstunas, Ramona; Ikegami, Tetsuro.

In: Antiviral Research, Vol. 98, No. 2, 2013, p. 135-143.

Research output: Contribution to journalArticle

Gowen, Brian B. ; Bailey, Kevin W. ; Scharton, Dionna ; Vest, Zachery ; Westover, Jonna B. ; Skirpstunas, Ramona ; Ikegami, Tetsuro. / Post-exposure vaccination with MP-12 lacking NSs protects mice against lethal Rift Valley fever virus challenge. In: Antiviral Research. 2013 ; Vol. 98, No. 2. pp. 135-143.
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