High seroprevalence and high risk: why are older adults more prone to respiratory syncytial virus?

Despite widespread seropositivity, respiratory syncytial virus (RSV) remains a major cause of severe illness in adults aged 60 years and older. This review examines why infection-acquired immunity fails to protect this group, focusing on four key factors: structural lung decline, comorbidities, immunosenescence, and impaired antibody responses. Age-related changes weaken mechanical defenses and antiviral immunity, while chronic diseases amplify RSV risk. Critically, repeated RSV infections may preferentially boost non-neutralizing antibodies targeting the postfusion F protein, limiting protection and possibly enhancing disease. The review also highlights how newly approved vaccines, based on stabilized prefusion F protein, can overcome these barriers by inducing strong neutralizing responses, offering a targeted strategy to reduce RSV burden in older adults.