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.