Safety of a mutagen-attenuated Rift valley fever virus vaccine in fetal and neonatal bovids

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. Animals - 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. Procedure - 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 ≤ 1:20 st 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. Post-parturient 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.