A single-cycle replicable Rift Valley fever phlebovirus vaccine carrying a mutated NSs confers full protection from lethal challenge in mice

Kaori Terasaki, Terry L. Juelich, Jennifer K. Smith, Birte Kalveram, David D. Perez, Alexander Freiberg, Shinji Makino

Research output: Contribution to journalArticle

Abstract

Rift Valley fever phlebovirus (RVFV) is a pathogen of Rift Valley fever, which is a mosquito-borne zoonotic disease for domestic livestock and humans in African countries. Currently, no approved vaccine is available for use in non-endemic areas. The MP-12 strain is so far the best live attenuated RVFV vaccine candidate because of its good protective efficacy in animal models. However, there are safety concerns for use of MP-12 in humans. We previously developed a single-cycle replicable MP-12 (scMP-12) which lacks NSs gene and undergoes only a single round of viral replication because of its impaired ability to induce membrane-membrane fusion. In the present study, we generated an scMP-12 mutant (scMP-12-mutNSs) carrying a mutant NSs, which degrades double-stranded RNA-dependent protein kinase R but does not inhibit host transcription. Immunization of mice with a single dose (105 PFU) of scMP-12-mutNSs elicited RVFV neutralizing antibodies and high titers of anti-N IgG production and fully protected the mice from lethal wild-type RVFV challenge. Immunogenicity and protective efficacy of scMP-12-mutNSs were better than scMP-12, demonstrating that scMP-12-mutNSs is a more efficacious vaccine candidate than scMP-12. Furthermore, our data suggested that RVFV vaccine efficacy can be improved by using this specific NSs mutant.

Original languageEnglish (US)
Article number17097
JournalScientific Reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

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Phlebovirus
Rift Valley Fever
Vaccines
eIF-2 Kinase
Membrane Fusion
Double-Stranded RNA
Zoonoses
Livestock
Neutralizing Antibodies
Culicidae
Immunization
Animal Models
Safety
Membranes

ASJC Scopus subject areas

  • General

Cite this

A single-cycle replicable Rift Valley fever phlebovirus vaccine carrying a mutated NSs confers full protection from lethal challenge in mice. / Terasaki, Kaori; Juelich, Terry L.; Smith, Jennifer K.; Kalveram, Birte; Perez, David D.; Freiberg, Alexander; Makino, Shinji.

In: Scientific Reports, Vol. 8, No. 1, 17097, 01.12.2018.

Research output: Contribution to journalArticle

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