DOI: 10.1128/mbio.00253-26 ISSN: 2150-7511
Maternal vaccination protects dams and prevents
in utero
transmission of Rift Valley fever virus in rats
Austin T. Hertel, Cynthia M. McMillen, Ryan M. Hoehl, Zachary D. Frey, Anita K. McElroy, Amy L. Hartman ABSTRACT
In utero
transmission and spontaneous fetal death are hallmarks of Rift Valley fever virus (RVFV) infection in pregnant animals. Compounding evidence indicates pregnant individuals are particularly vulnerable to RVFV, as
in utero
transmission and increased rates of miscarriage have been reported in people infected during pregnancy. Further, human placenta explants are permissive to RVFV infection. Viable vaccine candidates intended for veterinary or human use must protect vulnerable populations, including pregnant individuals and fetuses. Using a pregnant rat model, we show that maternal vaccination with a live-attenuated RVFV lacking the non-structural proteins NSs and NSm (RVFV-delNSs/NSm) is immunogenic, safe, and protective. Dams vaccinated either prior to or during pregnancy were protected from virulent challenge during pregnancy, and we found no evidence of infectious virus in the placentas and fetuses of challenged animals. These studies offer important pre-clinical data in a tractable pregnancy model and serve as a blueprint for evaluating future vaccine approaches designed to protect pregnant individuals and their fetuses.
IMPORTANCE
Rift Valley fever virus (RVFV) poses a formidable threat to pregnant animals and potentially to pregnant individuals and their developing fetuses. Despite this risk, pregnant individuals are rarely included in vaccine trials, leaving this potentially vulnerable population unprotected. Using a live-attenuated RVFV vaccine, we demonstrate that maternal vaccination is safe and protects both pregnant rats and their fetuses from congenital Rift Valley fever. Because live-attenuated vaccines are often contraindicated during pregnancy due to theoretical safety concerns, we further show that vaccination prior to pregnancy provides equivalent protection throughout future pregnancy. Taken together, these findings provide a blueprint for the preclinical evaluation of RVFV vaccines during pregnancy.