Project Details

Investigating the prevention of adverse fetal outcomes following vaccination with a ZIKV mRNA vaccine in mice

Megan Carey, MD, CTropMed

Summary

BACKGROUND: Congenital Zika Syndrome (CZS) interrupts neurodevelopment causing spontaneous abortion, contractures, and neurodevelopmental anomalies in children. Zika virus (ZIKV) is an arthropod-borne virus spread by Aedes mosquitoes. Two-thirds of the world’s population are exposed to Aedes mosquitoes. Climate change is increasing Aedes range and ZIKV outbreak potential. GAP: There are no therapeutics for CZS and a vaccine for ZIKV is urgently needed to prevent maternal infection and devastating neurodevelopmental disabilities in children. HYPOTHESIS: Our mRNA-lipid nanoparticle vaccine against the ZIKV envelope (Env) protein will be a safe and immunogenic maternal vaccine mitigating adverse fetal outcomes in mice. METHODS: We will vaccinate pregnant mice with two doses of our ZIKV-Env mRNA vaccine and compare litter sizes and pup clinical scores to measure the safety of our vaccine. To assess the prevention of fetal infection we will vaccinate female mice and infect them soon after becoming pregnant. Differences in litter sizes, clinical scores, viremia, and organ involvement will be used to measure vaccine efficacy. Additionally, we will assess rates of pup reabsorption by placental MRI to represent prevention of spontaneous abortion in humans. RESULTS: Pending. IMPACT: This study will address gaps in flavivirus vaccine research looking at the prevention of fetal adverse outcomes with an innovative imaging modality. Results of this study will be a step forward in preventing a congenital infection of global concern and toward a vaccine which could be implemented in outbreak settings.