Immunogenicity, Reactogenicity, and Safety of AS01E-adjuvanted Respiratory Syncytial Virus (RSV) Prefusion F Protein-based Candidate Vaccine (RSVPreF3 OA) When Co-administered With a Seasonal Quadrivalent Influenza Vaccine in Older Adults: Results of a Phase 3, Open-Label, Randomized Controlled Trial

Abstract

Abstract Background Co-administration of vaccines against respiratory syncytial virus (RSV) and influenza can be considered given their overlapping seasonality and may increase vaccine uptake and compliance. In this phase 3, open-label, randomized study, we evaluated the immunogenicity, reactogenicity, and safety of the AS01E-adjuvanted RSV prefusion F protein–based candidate vaccine (RSVPreF3 OA) when co-administered with a seasonal quadrivalent influenza vaccine (FLU-QIV) in older adults. Methods Participants aged ≥60 years (randomized 1:1) received either RSVPreF3 OA and FLU-QIV simultaneously on day 1 (Co-Ad group) or FLU-QIV on day 1 followed by RSVPreF3 OA on day 31 (sequential administration [SA] group). The co-primary objectives were to demonstrate noninferiority of RSVPreF3 OA in terms of RSV-A neutralization geometric mean titer (GMT) ratio and FLU-QIV in terms of hemagglutination inhibition GMT ratio for each FLU-QIV strain, when co-administered versus when administered alone at 1 month post-vaccination. Noninferiority was demonstrated if the upper limit of the 95% confidence interval of the group GMT ratio (SA/Co-Ad) was ≤1.5. Secondary descriptive objectives comprised additional immunogenicity assessments, reactogenicity, and safety. Results Of the 885 participants who received 1 dose of the study vaccines, 837 were included in the per protocol set. Demographic and baseline characteristics were balanced between the groups. Both co-primary objectives were met for both vaccines. Reported adverse events in both groups were mild to moderate, with a low frequency of grade 3 events. Conclusions Data from this study demonstrate that RSVPreF3 OA can be co-administered with FLU-QIV. Co-administration is well tolerated, with an acceptable safety profile. Clinical Trials Registration. NCT04841577.