RSV and COVID-19 Vaccine Coadministration in Adults 50 and Older: RSV Antibody Noninferiority Met, COVID-19 Criterion Not Met
Background and challenges
In a trial evaluating coadministration of a specific respiratory syncytial virus (RSV) vaccine and a COVID-19 vaccine in adults aged 50 years and older, the RSV neutralizing antibody response met the noninferiority criterion compared with sequential vaccination. The COVID-19 neutralizing antibody response narrowly missed the criterion, while investigators considered safety acceptable. These findings did not directly establish protection against infection or hospitalization.
The central question was whether giving the two vaccines together would cause interference between their immune responses. Investigators evaluated the combination of RSVPreF3, an RSV prefusion F protein vaccine containing the AS01E adjuvant, and an Omicron XBB.1.5-based COVID-19 messenger RNA (mRNA) vaccine.
Study design and key immune response findings
This was a phase 3, open-label, multicenter, randomized trial. Participants were assigned 1:1 to coadministration or a control group receiving the two vaccines sequentially, approximately one month apart. A total of 833 participants received vaccination: 417 in the coadministration group and 416 in the sequential vaccination group.
The primary outcomes were neutralizing antibody responses to RSV-A, RSV-B, and the virus that causes COVID-19 one month after vaccination. Investigators compared the ratio of the adjusted geometric mean titer (GMT) in the sequential vaccination group to that in the coadministration group. Noninferiority was defined as an upper bound of the 95% confidence interval for this ratio of 1.50 or less, indicating that any reduction in the antibody response with coadministration remained within the prespecified acceptable margin.
The GMT ratio was 1.12 (95% confidence interval, 0.97–1.28) for RSV-A and 1.08 (0.94–1.23) for RSV-B; both met the criterion. For Omicron XBB.1.5, the ratio was 1.31 (1.13–1.51). The upper confidence bound of 1.51 exceeded the threshold of 1.50, so noninferiority was not demonstrated. This does not mean that the antibody titer itself exceeded a threshold; it is a statistical judgment comparing antibody responses between the two vaccination schedules.
Safety, implications, and remaining questions
Among the prespecified symptoms assessed within four days after vaccination, the most common were injection-site pain, muscle pain, and fatigue. Most were mild or moderate, and the median duration of symptoms overall was three days or less, with similar durations in both groups. Safety was assessed through six months after vaccination. Adverse events reported beyond the prespecified symptoms, as well as serious adverse events, were generally balanced between groups. The abstract did not report the incidence of individual adverse events.
Investigators interpreted the narrow miss on the COVID-19 noninferiority criterion as not suggesting clinically meaningful immune interference and said the findings support coadministration of the two vaccines. However, that interpretation should be distinguished from the finding that noninferiority was not demonstrated. The available evidence concerns antibody responses to this vaccine combination and safety during the observation period; it does not establish protection against infection or hospitalization, or improved vaccination rates. The abstract alone cannot determine whether the same findings apply to other age groups or vaccine combinations.
The study design and results are available in the Clinical Infectious Diseases article abstract.
EMOTION_TAG: clinical
BACKGROUND: This trial evaluated co-administration of the AS01E-adjuvanted respiratory syncytial virus (RSV) prefusion F protein-based vaccine (adjuvanted RSVPreF3) and an Omicron XBB.1.5-based COVID-19 mRNA vaccine in ≥50-year-olds. METHODS: This phase 3, open-label, multi-center trial randomized ≥50-year-olds 1:1 to co-administration (Co-Ad group) or sequential administration approximately one month apart (Control group) of adjuvanted RSVPreF3 and the COVID-19 mRNA vaccine. Primary objectives were to demonstrate non-inferiority of humoral immune responses at one month post-vaccination in terms of RSV-A, RSV-B, and SARS-CoV-2 neutralizing titers, with the upper limit of the 95% confidence interval (CI) of adjusted geometric mean titer (GMT) group ratios (Control/Co-Ad) ≤1.50. Secondary objectives included assessment of reactogenicity up to four days and safety up to six months after vaccination. RESULTS: Overall, 833 participants were vaccinated (Co-Ad: 417; Control: 416). Non-inferiority was achieved for RSV-A (GMT ratio: 1.12 [95% CI: 0.97-1.28]) and RSV-B (GMT ratio: 1.08 [95% CI: 0.94-1.23]), and marginally missed for SARS-CoV-2 Omicron XBB.1.5 (GMT ratio: 1.31 [95% CI: 1.13-1.51]). Within four days post-vaccination, the most frequently reported solicited events were administration-site pain, myalgia, and fatigue. Most solicited events were of mild-to-moderate intensity, and the overall median duration was ≤three days and comparable between groups. Unsolicited and serious adverse events were generally balanced between groups. CONCLUSIONS: Adjuvanted RSVPreF3 co-administered with a COVID-19 mRNA vaccine maintained an acceptable safety profile in ≥50-year-olds. The marginal miss of the non-inferiority criterion for SARS-CoV-2 does not suggest clinically relevant interference. Therefore, the results support the co-administration of these vaccines.
These findings can inform discussions with adults aged 50 years and older about receiving this RSV vaccine and the XBB.1.5-based COVID-19 mRNA vaccine at the same visit. Clinicians can explain that the RSV antibody response met the noninferiority criterion, the COVID-19 antibody response did not, and describe the observed safety findings alongside these results. Coadministration could reduce the burden of separate visits, but this trial did not establish improved vaccination rates or fewer missed vaccinations. Antibody responses should not be equated with protection against infection or hospitalization. Actual vaccination decisions require separate consideration of current recommendations and individual circumstances; the provided abstract alone does not support recommending coadministration for every adult aged 50 years and older.