Vaccination in Pregnancy with the Bivalent Respiratory Syncytial Virus Vaccine Elicits Significant Specific IgA, IgG, and Secretory Antibody Titers in Human Milk

Background and Objectives: The RSVpreF vaccine, licensed for the prevention of respiratory syncytial virus (RSV)-associated lower respiratory tract disease in infants <6 months via maternal immunization, protects infants through transplacental-transferred antibodies. Additional benefits may be conferred via vaccine-induced antibodies in human milk, but milk was not collected in clinical trials. Here, we implemented a longitudinal, observational study to characterize RSV-specific antibodies in milk of lactating individuals who did or did not receive RSVpreF in pregnancy. Methods: Between September 2023 and February 2025, milk samples were self-collected from 73 vaccinated and 28 unvaccinated consented individuals during the first month postpartum and frozen until assessment by Luminex-based multiplex immunoassays. This study compared milk immunoglobulin G (IgG), immunoglobulin A (IgA), and total secretory antibody titers against RSVpreF and RSV G between vaccinated and unvaccinated groups using linear models adjusted for maternal age, race/ethnicity, infant daycare attendance, and presence of older children in the home. As prespecified in the study’s statistical analysis plan, the threshold for significance in this interim analysis was set at <0.0001, after adjustment for the primary multiple endpoints. Results: Mean human milk IgA, IgG, and total secretory antibody titers to RSVpreF were found to be 11- to 31-fold higher in vaccinated versus unvaccinated individuals ( p -adjusted < 0.0001). Antibody titers to RSV G (not a vaccine antigen, therefore indicative of responses from prior RSV infection) were not different between groups. Conclusions: High vaccine-induced secretory antibodies may be particularly important since secretory antibody is the most durable antibody class in milk and mucosa and therefore most likely to provide ongoing protection for infants.