Safety and efficacy of a mutagen-attenuated Rift valley fever virus vaccine in cattle

Objective - To examine safety and efficacy of a mutagen-attenuated Rift Valley fever virus (RVFV) vaccine (RVF MP-12) in cattle. Animals - 38 pregnant cows, 14 steers, and 10 lactating dairy cows. Procedure-Pregnant cows in their third, fifth, or eighth month of gestation were vaccinated (1 ml of RVF MP-12 containing 5 log₁₀ plaque-forming units [PFU] of virus) and were monitored daily through parturition for signs of disease, viremia, and immunologic response. Additionally, 10 vaccinated pregnant cows were challenge inoculated with virulent RVFV at post-vaccination day (PVD) 30 and were monitored daily for untoward effects. Ten unvaccinated pregnant cows also were challenge inoculated with virulent RVFV and served as challenge controls. Vaccinated lactating dairy cows were monitored for viremia and virus shedding in the milk through PVD 14. Yearling steers were vaccinated to assess their immunologic response to various doses of vaccine and were challenge inoculated with virulent RVFV at PVD 28 to assess protection. Results - 10 of 38 (26.3%) cows vaccinated during pregnancy developed transient postvaccination viremia titer ≤ 2.5 log₁₀ PFU/ml of serum. All vaccinated cows delivered live, healthy calves that were RVFV seronegative at birth, but which quickly acquired colostral antibodies. Vaccinated cows and their fetuses were protected when challenge exposed with virulent RVFV at PVD 30, whereas unvaccinated pregnant cows inoculated with RVFV became febrile and viremic, and aborted. Vaccine virus was unsuccessfully sought from milk of lactating dairy cows after vaccination, suggesting that shedding of vaccine virus through milk should not be a concern. Steers, inoculated with tenfold escalating vaccine doses, beginning with 1.0 log₁₀ PFU, were protected against virulent RVFV challenge exposure. Conclusions - RVF MP-12 may be safe and efficacious for use in pregnant or lactating bovids, and a minimal dose of vaccine may provide suitable protection against viremia.