RESUMEN
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 interview 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 one 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. CLINICALTRIALS.GOV REGISTRATION: NCT04841577.
RESUMEN
BACKGROUND: We evaluated co-administration of adjuvanted seasonal quadrivalent influenza vaccine (FLU-aQIV) and respiratory syncytial virus (RSV) prefusion F protein-based vaccine (RSVPreF3 OA) in ≥65-year-olds. METHODS: This phase 3, open-label trial randomized ≥65-year-olds to receive FLU-aQIV and RSVPreF3 OA concomitantly (Co-Ad) or sequentially, 1 month apart (Control). Primary objectives were to demonstrate the non-inferiority of FLU-aQIV and RSVPreF3 OA co-administration versus sequential administration in terms of hemagglutination inhibition (HI) titers for each FLU-aQIV strain and RSV-A and RSV-B neutralization titers, 1 month post-vaccination. Reactogenicity and safety were also assessed. RESULTS: Overall, 1045 participants were vaccinated (Co-Ad: 523; Control: 522). Non-inferiority of FLU-aQIV and RSVPreF3 OA co-administration versus sequential administration was demonstrated in terms of HI titers for the A/Victoria(H1N1), B/Victoria, and B/Yamagata influenza strains and RSV-A neutralization titers (upper limits [ULs] of 95% confidence intervals [CIs] for adjusted geometric mean titer [GMT] ratios [Control/Co-Ad] ≤1.50) but not for A/Darwin(H3N2) HI titers (95% CI UL = 1.53). The immune response to A/Darwin(H3N2) was further assessed post-hoc using a microneutralization assay; the post-vaccination adjusted GMT ratio (Control/Co-Ad) was 1.23 (95% CI: 1.06-1.42, ie, UL ≤1.50), suggesting an adequate immune response to A/Darwin(H3N2) following co-administration. RSV-B neutralization titers were comparable between groups (95% CI UL for adjusted GMT ratio ≤1.50). Solicited adverse events were mostly mild or moderate and transient; unsolicited and serious adverse event rates were balanced between groups. CONCLUSIONS: Adjuvanted FLU-aQIV and RSVPreF3 OA had acceptable reactogenicity/safety profiles when co-administered in ≥65-year-olds, without clinically relevant interference with the immune responses to either vaccine. CLINICAL TRIALS REGISTRATION: NCT05568797.