(665) Widespread maternal immunity to RSV suggests naturally-occurring antibodies provide incomplete neonatal protection: implications for vaccination

Objective: RSV vaccination in pregnancy was recently demonstrated to significantly reduce neonatal morbidity and mortality from RSV infection. The known vulnerability of neonates to severe RSV disease suggests that either many pregnant individuals do not have anti-RSV antibodies, or the antibodies from natural infection do not confer protection against severe disease for all infants. Understanding maternal antibody response is critical to informing vaccination strategies that optimize neonatal protection, we sought to evaluate maternal immunity and transplacental transfer of maternal IgG from natural RSV infection in a large cohort of pregnant individuals.

Study Design: Antibodies against RSV subtypes A and B pre-and post-fusion protein (RSV-F) were assayed in the plasma of 303 pregnant participants from geographically-distinct pregnancy cohorts, spanning all 3 trimesters of pregnancy, with a Luminex assay. In a subset of 126 participants, transplacental transfer of maternal anti-RSV IgG was assessed in paired maternal-cord plasma. Differences between IgG levels in maternal-cord pairs was determined by Wilcoxon signed rank tests.

Results: Anti-RSV-F IgG1 was detectable in 99.6% (302/303) maternal and 100% (126/126) cord samples. All anti-RSV-F IgG subclasses were present in the majority of mothers (Fig 1A). IgG levels were stable across trimesters of pregnancy (Fig 1B). In the 126 maternal-cord pairs, anti-RSV IgG was efficiently transferred across the placenta in 99.2% (125/126) of pairs (Fig 1C). IgG1 transferred most efficiently (mean cord:maternal ratio of 1.7, Fig 1D).

Conclusion: Across multiple pregnancy cohorts, nearly all pregnant individuals have anti-RSV-F IgG that crosses the placenta and is detectable in cord blood. These findings suggest that naturally-acquired maternal antibodies do not confer complete protection to neonates.   Understanding how antibody characteristics differ between naturally-acquired infection and vaccination in pregnant individuals is critical for the future optimization of maternal vaccination aimed at neonatal health.