P4.026: RSV Immunoprophylaxis in Infants and Breakthrough Infection: Clinical Impact and Viral Features

Background: Respiratory Syncytial Virus (RSV) is a leading cause of severe respiratory infections in infants. While new immunoprophylactic strategies (maternal vaccination [Abrysvo] and infant monoclonal treatment [nirsevimab]) mitigate disease burden in young infants, viral characteristics of breakthrough RSV infection have not been described.

Methods: Nasopharyngeal swabs were collected from all RSV-infected children ages < 2.0 years presenting for medical care at MGH between 9/2024-2/2025. RSV viral PCR cycle thresholds, genome sequences, and neutralization capacity, plus clinical outcomes, were assessed. Viral characteristics of infants immunized in the between 8/2024-2/2025 (current RSV season) were compared to those with no immunoprophylaxis or remote immunoprophylaxis administered prior to 4/2024. Analysis was completed by ANOVA, Fisher’s exact test and logistic regression with z-scores.

Results: We collected 216 RSV samples; 19 (9%) were from infants with current RSV immunoprophylaxis presented for medical attention, while 197 (91%) were from infants with remote or absent immunoprophylaxis. Infants with active RSV immunoprophylaxis had higher Ct values (less virus detected) than infants with remote/prior year immunoprophylaxis (p = 0.03) or no immunoprophylaxis (p = 0.03). RSV subtype A was the most frequently detected viral subtype in infants both with and without RSV immunoprophylaxis; however, neither RSV subtype A nor B impacted Ct values. While infants with active immunoprophylaxis were less likely to present for medical evaluation, of those who did seek medical attention, rates of hospitalization were comparable to the unvaccinated cohort suggesting alternative factors, such as prematurity, complex medical history, or immune responses contributed to severity of RSV infection. Respiratory symptoms and need for antibiotic use were lower in infants with active RSV immunoprophylaxis. Viral genome analysis and neutralization assays are underway. Immunoprofiling of these infants is ongoing to better understand the immune responses across prophylaxis groups.

Conclusion: RSV immunoprophylaxis reduces disease severity, viral burden, and need for antibiotics at time of RSV infection. Specific viral subtypes do not appear to drive breakthrough RSV infection. Analyses are underway to further characterize viral traits in breakthrough RSV infection. These data support clinical benefit in offering RSV immunoprophylaxis in pregnant mothers or to infants born during the RSV season.