title: Development of a novel, single-cycle replicable rift valley Fever vaccine.
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.
authors.affiliation: Department of Microbiology and Immunology, the University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Shin
authors.initials: S
authors.lastname: Murakami
authors.affiliation: Department of Microbiology and Immunology, the University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Kaori
authors.initials: K
authors.lastname: Terasaki
authors.affiliation: Department of Pathology, the University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Sydney I
authors.initials: SI
authors.lastname: Ramirez
authors.affiliation: Department of Microbiology and Immunology, the University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: John C
authors.initials: JC
authors.lastname: Morrill
authors.affiliation: Department of Microbiology and Immunology, the University of Texas Medical Branch, Galveston, Texas, United States of America; Center for Biodefense and Emerging Infectious Diseases, the University of Texas Medical Branch, Galveston, Texas, United States of America; UTMB Center for Tropical Diseases, the University of Texas Medical Branch, Galveston, Texas, United States of America; Sealy Center for Vaccine Development, the University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Shinji
authors.initials: S
authors.lastname: Makino
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D012295:Rift Valley Fever / Q000517:prevention & control*; D012296:Rift Valley fever virus / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D016019:Survival Analysis; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology*; D053586:Virus Internalization; D014779:Virus Replication
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D050505:Mutant Proteins; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; D014764:Viral Proteins; D014765:Viral Vaccines