title: Recombinant Rift Valley fever vaccines induce protective levels of antibody in baboons and resistance to lethal challenge in mice.
abstract: Rift Valley fever (RVF) is a zoonotic disease endemic in Africa and the Arabian Peninsula caused by the highly infectious Rift Valley fever virus (RVFV) that can be lethal to humans and animals and results in major losses in the livestock industry. RVF is exotic to the United States; however, mosquito species native to this region can serve as biological vectors for the virus. Thus, accidental or malicious introduction of this virus could result in RVFV becoming endemic in North America. Such an event would likely lead to significant morbidity and mortality in humans, and devastating economic effects on the livestock industry. Currently, there are no licensed vaccines for RVF that are both safe and efficacious. To address this issue, we developed two recombinant RVFV vaccines using vaccinia virus (VACV) as a vector for use in livestock. The first vaccine, vCOGnGc, was attenuated by the deletion of a VACV gene encoding an IFN-γ binding protein, insertional inactivation of the thymidine kinase gene, and expression of RVFV glycoproteins, Gn and Gc. The second vaccine, vCOGnGcγ, is identical to the first and also expresses the human IFN-γ gene to enhance safety. Both vaccines are extremely safe; neither resulted in weight loss nor death in severe combined immunodeficient mice, and pock lesions were smaller in baboons compared with the controls. Furthermore, both vaccines induced protective levels of antibody titers in vaccinated mice and baboons. Mice were protected from lethal RVFV challenge. Thus, we have developed two safe and efficacious recombinant vaccines for RVF.
authors.affiliation: International Laboratory of Molecular Biology for Tropical Disease Agents, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
authors.forename: James F
authors.initials: JF
authors.lastname: Papin
authors.forename: Paulo H
authors.initials: PH
authors.lastname: Verardi
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Jones
authors.forename: Francisco
authors.initials: F
authors.lastname: Monge-Navarro
authors.forename: Aaron C
authors.initials: AC
authors.lastname: Brault
authors.forename: Michael R
authors.initials: MR
authors.lastname: Holbrook
authors.forename: Melissa N
authors.initials: MN
authors.lastname: Worthy
authors.forename: Alexander N
authors.initials: AN
authors.lastname: Freiberg
authors.forename: Tilahun D
authors.initials: TD
authors.lastname: Yilma
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood* / Q000276:immunology; D002522:Chlorocebus aethiops; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D048548:Papio cynocephalus; D012295:Rift Valley Fever / Q000097:blood* / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D012296:Rift Valley fever virus; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D014616:Vaccinia virus; D014709:Vero Cells; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*
chemical_list: D000914:Antibodies, Viral; D006023:Glycoproteins; D014614:Vaccines, Synthetic; D014764:Viral Proteins; D014765:Viral Vaccines