title: Rift Valley fever virus vaccine lacking the NSs and NSm genes is safe, nonteratogenic, and confers protection from viremia, pyrexia, and abortion following challenge in adult and pregnant sheep.
abstract: Rift Valley fever virus (RVFV) is a mosquito-borne human and veterinary pathogen causing large outbreaks of severe disease throughout Africa and the Arabian Peninsula. Safe and effective vaccines are critically needed, especially those that can be used in a targeted one-health approach to prevent both livestock and human disease. We report here on the safety, immunogenicity, and efficacy of the ΔNSs-ΔNSm recombinant RVFV (rRVFV) vaccine (which lacks the NSs and NSm virulence factors) in a total of 41 sheep, including 29 timed-pregnant ewes. This vaccine was proven safe and immunogenic for adult animals at doses ranging from 1.0 × 10(3) to 1.0 × 10(5) PFU administered subcutaneously (s.c.). Pregnant animals were vaccinated with 1.0 × 10(4) PFU s.c. at day 42 of gestation, when fetal sensitivity to RVFV vaccine-induced teratogenesis is highest. No febrile reactions, clinical illness, or pregnancy loss was observed following vaccination. Vaccination resulted in a rapid increase in anti-RVFV IgM (day 4) and IgG (day 7) titers. No seroconversion occurred in cohoused control animals. A subset of 20 ewes progressed to full-term delivery after vaccination. All lambs were born without musculoskeletal, neurological, or histological birth defects. Vaccine efficacy was assessed in 9 pregnant animals challenged at day 122 of gestation with virulent RVFV (1.0 × 10(6) PFU intravenously). Following challenge, 100% (9/9) of the animals were protected, progressed to full term, and delivered healthy lambs. As expected, all 3 sham-vaccinated controls experienced viremia, fetal death, and abortion postchallenge. These results demonstrate that the ΔNSs-ΔNSm rRVFV vaccine is safe and nonteratogenic and confers high-level protection in sheep.
authors: Viral Special Pathogens Branch, Division of High Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, 1600 Clifton Road, MS G-14, Atlanta, GA 30329, USA.
authors: Brian H
authors: BH
authors: Bird
authors: Louis H
authors: LH
authors: Maartens
authors: Shelley
authors: S
authors: Campbell
authors: Baltus J
authors: BJ
authors: Erasmus
authors: Bobbie R
authors: BR
authors: Erickson
authors: Kimberly A
authors: KA
authors: Dodd
authors: Christina F
authors: CF
authors: Spiropoulou
authors: Deborah
authors: D
authors: Cannon
authors: Clifton P
authors: CP
authors: Drew
authors: Barbara
authors: B
authors: Knust
authors: Anita K
authors: AK
authors: McElroy
authors: Marina L
authors: ML
authors: Khristova
authors: César G
authors: CG
authors: Albariño
authors: Stuart T
authors: ST
authors: Nichol
mesh_terms: D000818:Animals; D000013:Congenital Abnormalities / Q000517:prevention & control / Q000662:veterinary; D005260:Female; D005334:Fever / Q000517:prevention & control / Q000662:veterinary; D017353:Gene Deletion; D006801:Humans; D007279:Injections, Subcutaneous; D011247:Pregnancy; D012295:Rift Valley Fever / Q000517:prevention & control / Q000662:veterinary*; D012296:Rift Valley fever virus / Q000235:genetics / Q000276:immunology*; D012756:Sheep; D012757:Sheep Diseases / Q000276:immunology / Q000517:prevention & control*; 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; D017361:Viral Nonstructural Proteins / Q000235:genetics; D014765:Viral Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000235:genetics / Q000276:immunology*; D014766:Viremia / Q000517:prevention & control / Q000662:veterinary
chemical_list: D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; D017361:Viral Nonstructural Proteins; D014765:Viral Vaccines