Nasal Mucosal Immunity is Associated with Protection against RSV Illness in Infants

Background. Despite advances in respiratory syncytial virus (RSV) immunoprophylaxis, RSV remains a leading cause of severe respiratory illness in infants. Immunity at the site of infection is potentially important yet airway mucosal immunity against RSV infection remains poorly defined. Methods. We collected nasal and blood samples across three pediatric cohorts: 1) children presenting to the emergency department with respiratory symptoms; 2) infants and mothers presenting to an urban hospital system across the RSV season; 3) infants born to mothers vaccinated with maternal pre-Fusion (F) vaccine. We analyzed mucosal and serologic anti-RSV antibodies and assessed for factors impacting titer magnitude and durability. Results. Specimens from 285 infants/young children and 39 mothers were analyzed. Mucosal anti-RSV antibody levels were lower in infants presenting with RSV infection compared to age-matched controls both in infants experiencing their first viral season (p = 0.0011) and older children (p < 0.0001). Higher levels of mucosal antibodies were seen in infants whose mothers received maternal pre-F vaccination, with IgG against RSV fusion protein tightly correlating between infant serum and nasal compartments (p < 0.0001). However, mucosal anti-RSV IgG waned significantly by 6 months of age (p < 0.0001). Conclusions. Higher mucosal anti-RSV antibody levels are associated with protection against RSV-related illness. Current immunoprophylactic strategies drive robust anti-RSV IgG responses in the infant mucosal and serological compartments; however, passive immunity wanes over 6 months. These results suggest that RSV immunization strategies optimizing durable mucosal immunity may protect infants from RSV-related respiratory illness.