Evaluation of Rift Valley fever vaccine candidates in pregnant rodent models

BackgroundRift Valley fever virus (RVFV) causes significant disease in humans and livestock. Immunogenicity of candidate vaccines rMP-12 and RVax-1 show promise, but their placental tropism and potential effects on fetal outcomes remain incompletely understood, particularly across different animal models. Understanding species-specific placental replication is essential to optimize vaccine safety in pregnant populations.ObjectiveTo evaluate the placental tropism and fetal outcomes of RVFV candidate vaccines rMP-12 and RVax-1 in pregnant Sprague–Dawley (SD) rats and C57BL/6 mice.MethodsPregnant SD rats and C57BL/6 mice were vaccinated intramuscularly at embryonic day 14 (E14) with 1 × 105 or 1 × 106 PFU of rMP-12 or RVax-1. Viral replication in maternal, placental, and fetal tissues was assessed at E18 in rats and at E17 or E19–21 in mice using viral RNA quantification and antigen detection. Fetal outcomes, including litter size, placental histopathology, and fetal demise, were recorded.ResultsIn rats, both vaccines showed minimal replication in placental and fetal tissues, indicating limited vertical transmission. In contrast, mice were more susceptible: viral RNA and antigens were detected in maternal livers, placentas, and fetal compartments. rMP-12–vaccinated mice showed reduced litter sizes and autolyzed placental tissues, whereas RVax-1–vaccinated mice exhibited fetal demise, with viral antigens detected in spongiotrophoblasts, syncytiotrophoblasts, and trophoblast giant cells of the junctional and labyrinth zones.ConclusionsRVFV vaccines rMP-12 and RVax-1 exhibit residual placental tropism in mice but minimal replication in rats, highlighting species-specific differences. Mouse models may be useful for studying placental tropism, and these findings inform future optimization of vaccine safety during pregnancy.