Development of a Novel, Single-Cycle Replicable Rift Valley Fever Vaccine

Shin Murakami, Kaori Terasaki, Sydney I. Ramirez, John C. Morrill, Shinji Makino

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Rift Valley fever virus (RVFV) (genus Phlebovirus, family Bunyaviridae) is an arbovirus that causes severe disease in humans and livestock in sub-Saharan African countries. Although the MP-12 strain of RVFV is a live attenuated vaccine candidate, neuroinvasiveness and neurovirulence of MP-12 in mice may be a concern when vaccinating certain individuals, especially those that are immunocompromised. We have developed a novel, single-cycle replicable MP-12 (scMP-12), which carries an L RNA, M RNA mutant encoding a mutant envelope protein lacking an endoplasmic reticulum retrieval signal and defective for membrane fusion function, and S RNA encoding N protein and green fluorescent protein. The scMP-12 underwent efficient amplification, then formed plaques and retained the introduced mutation after serial passages in a cell line stably expressing viral envelope proteins. However, inoculation of the scMP-12 into naïve cells resulted in a single round of viral replication, and production of low levels of noninfectious virus-like particles. Intracranial inoculation of scMP-12 into suckling mice did not cause clinical signs or death, a finding which demonstrated that the scMP-12 lacked neurovirulence. Mice immunized with a single dose of scMP-12 produced neutralizing antibodies, whose titers were higher than in mice immunized with replicon particles carrying L RNA and S RNA encoding N protein and green fluorescent protein. Moreover, 90% of the scMP-12-immunized mice were protected from wild-type RVFV challenge by efficiently suppressing viremia and replication of the challenge virus in the liver and the spleen. These data demonstrated that scMP-12 is a safe and immunogenic RVFV vaccine candidate.

Original languageEnglish (US)
Article numbere2746
JournalPLoS Neglected Tropical Diseases
Volume8
Issue number3
DOIs
StatePublished - 2014

Fingerprint

Rift Valley Fever
Rift Valley fever virus
Vaccines
RNA
Green Fluorescent Proteins
Phlebovirus
Bunyaviridae
Viral Envelope Proteins
Serial Passage
Arboviruses
Attenuated Vaccines
Replicon
Membrane Fusion
Viremia
Livestock
Mutant Proteins
Virus Replication
Neutralizing Antibodies
Endoplasmic Reticulum
Virion

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Infectious Diseases
  • Public Health, Environmental and Occupational Health

Cite this

Development of a Novel, Single-Cycle Replicable Rift Valley Fever Vaccine. / Murakami, Shin; Terasaki, Kaori; Ramirez, Sydney I.; Morrill, John C.; Makino, Shinji.

In: PLoS Neglected Tropical Diseases, Vol. 8, No. 3, e2746, 2014.

Research output: Contribution to journalArticle

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