Journal
ANTIVIRAL RESEARCH
Volume 98, Issue 2, Pages 135-143Publisher
ELSEVIER
DOI: 10.1016/j.antiviral.2013.03.009
Keywords
Rift Valley fever virus; Post-exposure vaccination; Phlebovirus; Viral hemorrhagic fever; Treatment
Categories
Funding
- National Institutes of Health [HHSN272201000039I]
- NIAID [R01 AI08764301-A1]
- Sealy Center for Vaccine Development at UTMB
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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)-beta 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. (C) 2013 Elsevier B.V. All rights reserved.
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