Abstract
An important goal of the Zika virus (ZIKV) vaccine is to prevent a congenital syndrome in fetuses of pregnant women, but studies directly evaluating maternal vaccination for ZIKV are lacking. Here we report maternal vaccination using a live-attenuated ZIKV vaccine (3ʹUTR-∆10-LAV) in a pregnant mouse model. Maternal immunization with 3ʹUTR-∆10-LAV does not cause any adverse effects on pregnancy, fetal development, or offspring behavior. One maternal immunization fully protects dams against ZIKV infection and in utero transmission. Although neutralizing antibody alone is sufficient to prevent in utero transmission, a higher neutralizing titer is required to protect pregnant mice against in utero transmission than that required to protect non-pregnant mice against viral infection. The immunized dams transfer maternal antibodies to pups, which protect neonates against ZIKV infection. Notably, pregnancy weakens maternal T cell response to 3ʹUTR-∆10-LAV vaccination. Our results suggest that, besides vaccinating non-pregnant individuals, 3ʹUTR-∆10-LAV may also be considered for maternal vaccination.
Highlights
An important goal of the Zika virus (ZIKV) vaccine is to prevent a congenital syndrome in fetuses of pregnant women, but studies directly evaluating maternal vaccination for ZIKV are lacking
ZIKV infection is associated with Guillain-Barré syndrome (GBS), an autoimmune disease that can lead to paralysis[4,5]
Could maternal vaccination protect against viral infection and in utero transmission? Does pregnancy affect immune responses to ZIKV vaccination? Does maternal immunity derived from vaccination during pregnancy protect newborns against infection? Do pregnant and nonpregnant individuals require different levels of immunity to prevent ZIKV infections? Is neutralizing antibody alone sufficient to prevent in utero transmission? The answers to these questions are critical to guide the clinical development and regulatory approval of ZIKV vaccines
Summary
In the mouse pregnancy model, E4.5 is the latest time that could be rationalized for maternal vaccination because (i) six days are needed to allow 3ʹUTR-Δ10-LAV to elicit protective immunity (Supplementary Fig. 1) and (ii) E10.5 is an optimal infection time to achieve analyzable fetal viral loads and developmental defects[15]. Challenge with ZIKV PRVABC59 did not significantly boost maternal neutralizing antibody titers in the 3ʹUTR-Δ10-LAV-vaccinated dams (Compare Supplementary Fig. 7b, i). Pregnant mice transfused with low levels of neutralizing antibodies (i.e., NT50 titers
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