title: Safety of a mutagen-attenuated Rift Valley fever virus vaccine in fetal and neonatal bovids.
abstract: OBJECTIVE
  To examine effects of in utero inoculation with a mutagen-attenuated Rift Valley fever virus (RVFV) vaccine (RVF MP-12) on fetal bovids and to assess the safety and efficacy of calfhood vaccination with RVF MP-12.
  
  
  METHODS
  18 pregnant Hereford and Hereford-type cows in the third or fifth month of gestation, their progeny, and 25 calves from cows immunized with RVF MP-12 during pregnancy.
  
  
  METHODS
  Bovine fetuses were inoculated, via laparotomy, with 1 ml of RVF MP-12 containing 5 log10 plaque-forming units (PFU) of virus. Blood was obtained from newborn calves prior to their ingestion of colostrum. Immune-naive calves and calves born to RVF MP-12-vaccinated dams, ranging in age from 2 to 45 days, were vaccinated with RVF MP-12, and some were later challenge exposed with 1 ml of 5.7 log10 PFU of virulent RVFV strain ZH-501. Cows were monitored for viremia and antibody responses and for hematologic and serum biochemical alterations through parturition or abortion.
  
  
  RESULTS
  Surviving in utero-vaccinated calves were healthy, with no noticeable defects. Except for 1 vaccine-inoculated fetus that died on postinoculation day 21, all in utero-vaccinated fetuses had serum neutralizing antibody titer > or = 1:20 at the time of delivery. All dams of in utero-vaccinated fetuses also developed neutralizing antibody titer. Calves born to cows vaccinated during gestation did not have antibody at birth, and all but 1 quickly acquired colostral antibody. Postparturient inoculation of immune-naive calves and calves with colostral antibodies resulted in no untoward effects, and all calves with detectable neutralizing antibodies were protected against virulent virus challenge exposure.
  
  
  CONCLUSIONS
  Fetal death and abortion would be rare even if fetuses were exposed to RVF MP-12. The trauma and complications associated with in utero inoculation do not make this a practical method of immunization. RVF MP-12 was safe, immunogenic, and protective in calves as young as 2 days of age.
authors.affiliation: US Army Medical Research Institute of Infectious Diseases, Applied Research Division, Fort Detrick, Frederick, MD 21702-5011, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Morrill
authors.forename: C A
authors.initials: CA
authors.lastname: Mebus
authors.forename: C J
authors.initials: CJ
authors.lastname: Peters
mesh_terms: D000034:Abortion, Veterinary / Q000517:prevention & control; D000818:Animals; D000831:Animals, Newborn / Q000097:blood / Q000276:immunology*; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D002417:Cattle; D002418:Cattle Diseases / Q000453:epidemiology / Q000276:immunology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005313:Fetal Death / Q000517:prevention & control; D005315:Fetal Diseases / Q000453:epidemiology / Q000276:immunology / Q000517:prevention & control*; D007112:Immunity, Maternally-Acquired; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D009153:Mutagens; D009500:Neutralization Tests / Q000662:veterinary; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology / Q000517:prevention & control / Q000662:veterinary; D012295:Rift Valley Fever / Q000453:epidemiology / Q000276:immunology / Q000517:prevention & control*; D012296:Rift Valley fever virus / Q000276:immunology*; D014611:Vaccination / Q000379:methods / Q000662:veterinary*; D014613:Vaccines, Attenuated / Q000009:adverse effects / Q000276:immunology / Q000592:standards; D014765:Viral Vaccines / Q000009:adverse effects / Q000276:immunology / Q000592:standards*
chemical_list: D000914:Antibodies, Viral; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D009153:Mutagens; D014613:Vaccines, Attenuated; D014765:Viral Vaccines