Transamniotic fetal mRNA vaccination: Active immunization against Zika virus in a rodent model

We investigated whether transamniotic fetal mRNA vaccination could be a viable strategy for perinatal immunization against Zika virus (ZIKV) infection in a rodent model.

Twenty pregnant Sprague Dawley dams underwent volume-matched intra-amniotic injections in all their fetuses (n = 280) of either a suspension of a custom-made mRNA encoding for the ZIKV pre-membrane (ZIVK-prM) and envelope (ZIKV-E) structural proteins encapsulated in a semi-synthetic composite lipopolyplex (vaccinated, n = 153), or of the same lipopolyplex without mRNA (control, n = 127) on gestational day 17-18 (E17-18; term = E21-22). Pup serum levels of ZIKV-E antigen-specific IgG antibodies were measured by ELISA at term up to 3 months of age. Splenocyte and lymph node cell suspensions were incubated either with or without ZIKVE challenge, followed by flow cytometry to assess T-cell response.

When controlled by mRNA-free injections, ZIKV-E-specific IgG was not detected in the serum of term fetuses; however, levels were significantly elevated in vaccinated pups from postnatal day 5-16 (p = 0.005-0.002). Splenocytes from vaccinated pups showed significant increases in IL-6 and IFN- γ productions after the antigen-specific challenge at 2 and 3 months (p = 0.049 to 0.003 vs. nonchallenged cells), along with a significant decrease in IL-13 production at 3 months (p = 0.006). Lymph node cells also demonstrated increased production of IFN-γ (p < 0.001 vs. non-challenged cells), along with a significant decrease in IL-13 production, both at 3 months (p = 0.014).

Transamniotic fetal mRNA vaccination with a Zika virus antigen can induce adaptive humoral and cellular immune responses extending into the neonatal period in a healthy rat model.

N/A (animal and laboratory study).

Animal and laboratory study.