Breast milk prefusion F Immunoglobulin G as a correlate of protection against respiratory syncytial virus acute respiratory illness

Background: Transplacental RSV antibody transfer has been characterized, but little is known about the protective effect of breast milk RSV-specific antibodies. Serum antibodies against the prefusion RSV fusion protein (pre-F) exhibit high neutralizing activity. We investigate protection of breast milk pre-F antibodies against RSV acute respiratory infection (ARI). Methods: Breast milk at 1, 3, and 6 months postpartum and mid-nasal swabs during infant illness episodes were collected in mother-infant pairs in Nepal. 174 infants with and without RSV ARI were matched 1:1 by risk factors for RSV ARI. Pre-F IgA and IgG antibody levels were measured in breast milk. Results: The median breast milk pre-F IgG antibody concentration before illness was lower in mothers of infants with RSV ARI (1.4, IQR 1.1-1.6 log10 ng/mL) than without RSV ARI (1.5, IQR: 1.3-1.8 log10 ng/mL, p=0.001). There was no difference in median maternal pre-F IgA antibody concentrations in cases (1.7, IQR: 0.0-2.2 log10 ng/mL) versus controls (1.7, IQR: 1.2-2.2 log10 ng/mL, p=0.58). Conclusion: Low breast milk pre-F IgG antibodies before RSV ARI supports a potential role for pre-F IgG as a correlate of protection against RSV ARI. Induction of breast milk pre-F IgG may be a mechanism of protection for maternal RSV vaccines