Efficacy of emergency maternal MVA-ZIKV vaccination in a rapid challenge model of lethal Zika infection.

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.