A first-in-human Phase 1/1b randomized trial evaluating the safety and immunogenicity of a respiratory syncytial virus (RSV) virus-like particle subunit vaccine (IVX-121) in healthy young and older adults

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract disease in all age groups, with substantial burden in older adults. Here, we report the safety and immunogenicity of IVX-121, an investigational virus-like particle vaccine against RSV. This Phase 1/1b trial (EudraCT number: 2020-003633-38) randomized 90 healthy young (18–45 y of age; Phase 1) and 130 older adults (60–75 y of age; Phase 1b) to receive a single intramuscular injection of IVX-121 at low (25 µg), medium (75 µg), or high (250 µg) dose, with/without the adjuvant aluminum hydroxide (Al[OH]3), or placebo. Outcomes were assessed through Day 180. Older adult participants who had received IVX-121 or placebo could continue into an extension study in which safety was assessed for an additional 6 months before receiving IVX-121 (75 µg, unadjuvanted, open-label) on Day 365; safety and immunogenicity were assessed up to Day 546. Adverse reactions were generally mild, and there were no vaccine-related serious adverse events. All IVX-121 dose levels and formulations boosted preexisting RSV neutralizing antibody (nAb) responses. Although not statistically powered to compare treatment groups, there was no clear dose response and the adjuvant Al(OH)3 did not appear to improve immunogenicity. For both age groups, IVX-121 induced nAbs against RSV A and B, which remained above baseline levels for at least 6 months. A second dose of IVX-121 in older adults elicited a modest increase in nAbs against RSV A but not RSV B. Overall, IVX-121 had a favorable safety profile and induced immune responses against RSV in young and older adults.