Magnitude and durability of RSV-specific immune responses three years after hospitalization for RSV-associated acute respiratory illness among adults ≥50 years.

BACKGROUND: Understanding immune responses to RSV natural infection in older adults could help inform the need for vaccination, as neutralizing antibodies correlate with protection in this high-risk population. METHODS: Adults ≥50 years of age hospitalized with acute respiratory illness were prospectively enrolled (September 2018─March 2020) at two Atlanta, Georgia hospitals. Nasopharyngeal and oropharyngeal swabs were analyzed, and standard-of-care RSV results were recorded. Follow-up visits occurred in early convalescence (V2), at start of the next respiratory season (SS2), and 2- and 3-years post-infection. Sera were analyzed for RSV-binding IgG by enzyme immunoassay and RSV-A2 and -B1 by neutralization assays. Antibody decay was measured by linear regression of log2-transformed titers. PBMCs were analyzed for T-cell responses by intracellular cytokine staining. RESULTS: Nineteen RSV-positive and 11 RSV-negative participants were eligible for analysis. For RSV-positive participants, RSV IgG and neutralizing antibodies peaked in early convalescence, and gradually waned through 3-year follow-up. RSV IgG titers declined by -0.08 log2 per month, while RSV-A and -B neutralizing antibody titers declined by -0.05log2 per month and were statistically equivalent to RSV-negative participants by the SS2 visit. For RSV-negative participants, minimal changes in antibody titers were observed over time. No significant differences were seen in RSV-specific T cell responses from SS2 to 2- and 3-year follow-up among either group. CONCLUSIONS: RSV binding and neutralizing antibodies were transiently elevated following natural infection in older adults but waned to levels similar to RSV-negative participants by the next season's start. Vaccines that counter waning immunity are needed in this high-risk population.