Evaluation of Rift Valley fever vaccine candidates in pregnant rodent models

Abstract

Background: Rift 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.

Objective: To 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.

Methods: Pregnant 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.

Results: In 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.

Conclusions: RVFV 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.

Keywords: Live-attenuated vaccine; MP-12 vaccine; Mouse model; Placenta; Pregnancy; RVax-1 vaccine; Rat model; Reverse genetics; Rift Valley fever virus.