Fetal Secretory IgA Delivery via Transamniotic Fetal Immunotherapy (TRAFIT) in a Rodent Model

Abstract

PurposeWe sought to determine the feasibility and routing kinetics of transamniotic fetal delivery of secretory immunoglobulin-A (SIgA), in a rodent model. MethodsFetuses (n = 94) from seven time-dated pregnant dams received intra-amniotic injections on gestational day 17 (E17, term = E21–22) of either saline (n = 15) or a solution of 1 mg/mL of ≥95% homogeneous human SIgA (n = 79). Animals were euthanized daily at E18–E21 for quantification of the IgA component by ELISA at gestational membranes, placenta, and select fetal anatomical sites against saline controls procured at term. Statistical analysis was by Mann–Whitney U-test. ResultsNone of the saline-injected animals had detectable human IgA. SIgA-injected fetuses showed human IgA in the stomach aspirate, intestinal wall, lungs, liver, and serum at all time points. IgA levels were significantly higher in the gastric aspirate and in the intestine than in all other sites (p < 0.001 for both), with intestinal levels remaining stable through E18–E21 (p = 0.09–0.62 pairwise). Serum and placental levels were consistently low throughout, reaching near zero levels by E21. ConclusionsThe chronology of exogenous secretory-IgA kinetics after intra-amniotic injection is suggestive of fetal uptake by ingestion, leading to consistent levels in the gastrointestinal tract. Transamniotic fetal immunotherapy (TRAFIT) with secretory-IgA may become a novel strategy for enhancing early mucosal immunity. Level of EvidenceN/A (animal and laboratory study). Type of StudyAnimal and laboratory study.