Abstract
Zika virus (ZIKV) outbreak of 2015 was associated with microcephaly and congenital birth defects in children born to pregnant women infected with ZIKV. Using the highly susceptible Type I Interferon Receptor-deficient mouse-model, we demonstrate that a single emergency vaccination with a non-replicating MVA-ZIKV vaccine, when administered as early as 2-days before challenge fully protected non-pregnant and pregnant mice and fetuses against lethal ZIKV-infection. Early protection was associated with the rapid emergence of ZIKV-specific CD8+ T cell responses; depletion of CD8+ T cells resulted in the loss of protection supporting a critical role for CD8+ T cells in the early protective efficacy of MVA-ZIKV. Neutralizing antibody responses were induced later than the CD8+ T cell responses, suggesting that it may play a role in later stages of infection. Our results suggest that MVA-ZIKV induces potent anamnestic cellular immunity early after infection, contributing to its protective efficacy against rapid ZIKV challenge.