J Pediatr Surg. 2025 Aug 8:162516.
Abstract
Purpose: Modified monoclonal class-G immunoglobulins (IgG) have been shown to protect infants from respiratory syncytial virus (RSV), a prevalent disease with particularly high morbidity in newborns. We sought to determine whether a clinically relevant monoclonal IgG against RSV could be delivered to the fetus via transammiotic fetal immunotherapy (TRAFIT) and remain bioavailable after birth.
Methods: Fetuses (n=75) from five pregnant dams received volume-matched intra-amniotic injections on gestational day 17-18 (E17-18, term=E21-22) of either an FDA approved and commercially available recombinant human immunoglobulin-G1-kappa (IgG1κ) monoclonal antibody against RSV (Nirsevimab®) (n=30) or of saline (n=45), the latter to control for possible IgG1κ interspecies homology. Levels of IgG1κ were quantified by ELISA in the serum and lungs at term and on postnatal day of life 7 (P7). Maternal serum samples were also tested. Statistical analyses included two-tailed Fisher's exact test, Wilcoxon rank sum test, and mixed-effects median regression (p<0.05).
Results: Overall survival was not significantly different between the two groups (p=0.808). Levels of the IgG1κ monoclonal antibody were significantly higher than that of controls in serum and lung samples at both term and P7 (all p<0.001). IgG1k levels in maternal serum samples were not significantly different between the groups.
Conclusions: TRAFIT with a clinically relevant recombinant human monoclonal antibody against RSV leads to sustained levels of the antibody in the serum and lungs of the neonate at term and into the early neonatal period in a rat model. TRAFIT could become a viable option for the prevention against RSV in newborns.
Level of evidence: N/A (animal and laboratory study).
Products: DVV02802, Research Grade Nirsevimab
