A Novel Unadjuvanted Subunit Respiratory Syncytial Virus Prefusion F Vaccine Induces Potent and Differentiated Functional Immune Responses Compared to AS01-Adjuvanted Arexvy in Older Adults.

Background: Licensed recombinant protein respiratory syncytial virus (RSV) vaccines can prevent substantial morbidity in older adults. However, revaccination to prevent waning protection may be suboptimal, prompting the exploration of candidates for heterologous boosting. In this clinical trial of RSV vaccine-naive older adults, we evaluated SCB-1019T, a novel unadjuvanted bivalent RSV prefusion F (preF) protein vaccine stabilized via Trimer-Tag technology, in comparison to the licensed AS01 Methods: In this phase 1, randomized, placebo-controlled, observer-blind study, after proof-of-concept assessments in young adults (18-59 years) and older adults (60-85 years), we administered 1 dose of SCB-1019T (n = 30), Arexvy (n = 30), or placebo (n = 10) to older adults (60-85 years). Safety, reactogenicity, and immunogenicity were assessed up to 28 days postvaccination. Results: SCB-1019T had a more favorable local safety profile, with fewer recipients reporting injection-site reactions than Arexvy recipients (17% vs 77%), whereas systemic adverse events were similar (43% vs 50%, respectively). Injection-site reactions and systemic adverse events were mild and transient, and no safety concerns were identified for SCB-1019T or Arexvy. Importantly, SCB-1019T induced similar (∼7-fold) increases of RSV-A and RSV-B neutralizing antibody titers to Arexvy. Moreover, exploratory results indicated that SCB-1019T induced potent antibodies to 3 key neutralization epitopes. Conclusions: In older adults, SCB-1019T had an acceptable and favorable safety profile. The humoral immunogenicity SCB-1019T was similar to that of Arexvy, which contains the potent AS01