Enhanced placental antibody transfer efficiency with longer interval between maternal respiratory syncytial virus vaccination and birth

Abstract

Background: Respiratory syncytial virus is associated with significant neonatal and infant morbidity and mortality. Maternal bivalent respiratory syncytial virus prefusion F respiratory syncytial virus vaccination to protect neonates and infants was approved in September 2023 for administration between 32+0 and 36+6 weeks to protect neonates and infants. This approved timeframe is narrower than the 24 to 36 week window evaluated in the clinical trial, due to the possible association between preterm birth and vaccine administration. Currently, data are lacking on how maternal vaccine timing within the approved window affects the transfer of antibodies from mother to fetus, critical information that could influence clinical practice.

Objective: We sought to examine how gestational age at vaccination and time elapsed from maternal respiratory syncytial virus vaccination to delivery impacted transfer of maternal antibodies measured in the umbilical cord at delivery and in peripheral blood of 2-month infants. We also examined differences in maternal and cord respiratory syncytial virus antibody levels achieved by vaccination vs natural RSV infection.

Study design: A prospective cohort study was conducted at 2 academic medical centers between September 20, 2023 and March 21, 2024, enrolling 124 individuals who received the respiratory syncytial virus vaccine during pregnancy. Infant capillary blood was collected at 2 months of age from 29 of the infants. Maternal and cord immunoglobulin G levels achieved by respiratory syncytial virus vaccination were compared to those associated with maternal natural respiratory syncytial virus infection, using banked blood from 20 maternal:cord dyads collected prior to the availability of the maternal respiratory syncytial virus vaccine. Levels of immunoglobulin G against respiratory syncytial virus strain A2 and B fusion (F) and attachment (G) proteins and against pertussis toxin (as a comparator antigen from a vaccine routinely administered earlier in pregnancy) were measured using a Binding Antibody Multiplex Assay. Differences in titers between vaccination and natural infection were examined using Wilcoxon rank-sum test. Differences in cord:maternal transfer ratios and 2-month infant antibody levels by timing of maternal vaccination were evaluated by Kruskal-Wallis testing.

Results: Maternal respiratory syncytial virus vaccination resulted in significantly higher maternal and cord antirespiratory syncytial virus F antibody levels than natural infection (5.72 vs 4.82 log₁₀ mean fluorescence intensity, P<.0001 maternal; 5.81 vs 5.03 log₁₀ mean fluorescence intensity, P<.0001 cord). Maternal vaccination 2 to 3 weeks and 3 to 4 weeks prior to delivery was associated with significantly lower cord:maternal transfer ratios than were observed when vaccination occurred >5 weeks prior to delivery (P=.03 for 2-3 weeks, P=.007 for 3-4 weeks), and significantly lower transfer ratios than observed for pertussis vaccination administered prior to 30 weeks of gestation (P=.008 for 2-3 weeks, P=.03 for 3-4 weeks, similar at >4 weeks).

Conclusion: Vaccine administration earlier in the approved 32 to 36 week window (at least 5 weeks prior to delivery) results in the highest transplacental transfer of maternal antibodies to the neonate. These results should inform the counseling of pregnant individuals on optimal vaccination timing.

Keywords: Abrysvo; RSV; cord blood; maternal blood; neonatal immunity; transplacental transfer; vaccine.