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

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. © 2014 murakami et al.