Maternal RSV vaccination timing optimizes newborn immunity through improved antibody transfer

New findings reveal that maternal RSV vaccination timing is key to safeguarding newborns, with enhanced protection observed when the vaccine is administered early in the CDC-recommended window.

Study: Enhanced placental antibody transfer efficiency with longer interval between maternal RSV vaccination and birth (PDF). Image Credit: CI Photos / Shutterstock

In a recent study published in the American Journal of Obstetrics and Gynecology (PDF), researchers evaluated the transfer efficiency of maternal anti-respiratory syncytial virus (RSV) antibodies to unborn neonates in mothers with different vaccination statuses (unvaccinated versus vaccinated) and among various vaccination timing points (early versus late in the recommended vaccination window). They further evaluated neonatal outcomes associated with antibody transfer, examining correlations with morbidity and mortality based on these vaccination timing regimes.

Study findings revealed that maternal vaccination substantially increased anti-RSV antibody titers (both maternal and placental) compared to those derived from natural RSV infections, highlighting the importance of vaccine-induced immunity for both previously infected and uninfected mothers. While RSV-attachment protein concentrations were statistically similar across vaccinated and unvaccinated cohorts, the former cohort expressed substantially higher overall anti-RSV antibody titers.

Antibody transfer efficiency analyses revealed that maternal vaccinations administered earlier during the CDC-recommended 32-36 week gestational window (specifically at least five weeks prior to delivery) resulted in superior transfer efficiency to the fetus and improved associated neonatal outcomes. Vaccinations received five weeks or more prior to infant birth were observed to produce the best transfer outcomes.

Background

Respiratory syncytial virus (RSV) is a respiratory pathogen that causes a mild, cold-like infection in adults but can cause severe, potentially lethal infections in infants. RSV is estimated to affect between 2-3% of infants six months or younger and remains the leading cause of infant hospitalization (approximately 25%) in the United States. Notably, the prevalence of RSV in infants has been on the rise, expediting the need for effective prevention strategies in this vulnerable population.

Previous research on both RSV- and non-RSV-associated antibody transfer has shown that the placental transfer of antibodies from mothers to their unborn children plays a vital role in immunity. The MATISSE (Maternal Immunization Study for Safety and Efficacy) trial highlighted the benefits of RSV vaccination in pregnancy using the bivalent RSV prefusion F (RSVpreF) recombinant protein, which significantly reduced RSV risk in infants. Consequently, the US Centers for Disease Control and Prevention (CDC) recommended the vaccine’s use in pregnant women starting September 2023.

However, while the MATISSE study evaluated vaccination administration periods across a longer 24-36 week window, the CDC has recommended a shorter window of 32-36 weeks to address preterm birth concerns possibly associated with RSV vaccination. This narrower window might reduce the time for effective antibody transfer, thus potentially impacting vaccination efficacy and infant RSV risk. To date, the impacts of different vaccination periods on infant RSV outcomes remain insufficiently understood.

“As fewer than half the MATISSE trial participants received the RSVpreF vaccine during the now-recommended 32-36 week gestational period (1,628 of 3,568 participants), data are lacking on the impact of timing of maternal vaccination within this window on transplacental transfer of maternal antibody, a correlate of infant protection.”

About the study

The present study was designed to address preexisting gaps in knowledge about the relationship between vaccination period and RSV outcomes by comparing outcomes across a spectrum of vaccination statuses (unvaccinated versus vaccinated) and pregnancy durations (early versus late). These findings would inform prospective parents, healthcare providers, and public health agencies about the most effective approaches to optimize infant health.

Study data was obtained from two independent cohorts – Massachusetts General Hospital and Mount Sinai School of Medicine – comprising pregnant or postpartum (up to two months) adult (18 years and older) women (n = 122). In the vaccinated group, participants were included only if they had received the RSV vaccine (Abrysvo) during pregnancy. Additionally, for comparison, 20 unvaccinated women with naturally derived anti-RSV antibodies were included.

The researchers conducted sterile blood draws from umbilical cord blood and placental samples at both delivery admission and birth, then collected additional samples from 29 neonates to further assess RSV outcome characteristics. Using the Binding Antibody Multiplex Assay (BAMA), the study quantified immunoglobulin G (IgG) levels against three RSV proteins: anti-RSV strain A2 (A2), B fusion (F), and attachment (G) proteins.

Statistical analyses included a range of methods to ensure robust comparisons, such as Kruskal-Wallis and Dunn’s post hoc tests for between-group comparisons, Benjamini-Hochberg analysis for multiple comparisons, and Wilcoxon tests for paired and unpaired analyses. Transfer ratios (indicating the percentage of antibody transfer from mother to offspring) were computed using maternal plasma MFI readings. Linear mixed-effects models helped explore trends in vaccination acceptance during pregnancy and impacts on neonatal antibody transfer efficiency.

Study findings

The present study revealed three noteworthy findings. First, vaccinated participants had significantly higher overall (A2 + F + G) antibody titers compared to unvaccinated but previously RSV-infected mothers. Interestingly, G antibody titers were similar across vaccinated and unvaccinated groups, indicating that prior infection alone may be insufficient for strong protective antibody levels, emphasizing the need for vaccination regardless of RSV infection history.

Second, anti-RSV G protein titers in neonatal blood samples peaked at birth but showed a marked decline by two months of age. Vaccination-derived antibodies persisted longer and at higher concentrations than those from naturally acquired maternal infection.

Finally, the timing of vaccination was found essential for optimal antibody transfer efficiency, with intervals of five or more weeks from vaccination to birth yielding the best results. Conversely, shorter intervals (2-3 weeks) showed nearly half the transfer efficiency, highlighting the importance of vaccine timing within the CDC-recommended period.

Conclusions

The study underscores the importance of both maternal vaccination and strategic vaccination timing in achieving optimal anti-RSV antibody levels in neonates. Vaccine-derived antibodies not only surpassed those from prior RSV exposure but also demonstrated greater persistence, contributing to longer-lasting neonatal protection.

Notably, longer durations between vaccination and birth improved both transfer efficiency and neonatal outcomes. However, additional research on possible preterm delivery risks is warranted before making universal recommendations. These findings suggest that maternal vaccination administered at least five weeks prior to delivery may offer the best protection against infant RSV risk.