RSV and COVID-19 Vaccine Coadministration in Adults 50 Years and Older

Key Takeaways

• Noninferiority was achieved for RSV-A and RSV-B, while the upper bound of the 95% confidence interval for the Omicron XBB.1.5 SARS-CoV-2 comparison was just above the predefined cutoff.
• Same-visit vaccination was compared with sequential administration about one month apart, with neutralizing titers assessed one month after vaccination.
• Administration-site pain, myalgia, and fatigue were the most common solicited reactions within four days; most were mild to moderate and short-lived, and unsolicited and serious events were generally balanced.

In adults aged 50 years and older, same-visit coadministration preserved RSV immune responses, while the Omicron XBB.1.5 SARS-CoV-2 noninferiority endpoint narrowly missed its prespecified margin.

Investigators conducted a phase 3, open-label, multicenter, 1:1 randomized comparison in adults aged 50 years and older, assigning 417 to coadministration and 416 to sequential dosing about one month apart. The vaccines were the AS01E-adjuvanted RSV prefusion F protein vaccine, adjuvanted RSVPreF3, and the Omicron XBB.1.5-based COVID-19 mRNA vaccine. The primary objective was noninferiority for RSV-A, RSV-B, and SARS-CoV-2 neutralizing titers one month after vaccination.

For RSV-A, the adjusted geometric mean titer ratio was 1.12 with a 95% confidence interval of 0.97 to 1.28, which met the noninferiority margin. For RSV-B, the adjusted ratio was 1.08 with a 95% confidence interval of 0.94 to 1.23, also within the margin. For SARS-CoV-2 Omicron XBB.1.5, the adjusted ratio was 1.31 with a 95% confidence interval of 1.13 to 1.51, leaving the upper bound just above the prespecified cutoff. Investigators therefore recorded a narrowly missed prespecified noninferiority endpoint for SARS-CoV-2, while the RSV endpoints remained within bounds. The immunogenicity results separated into preserved RSV responses and a borderline SARS-CoV-2 finding.

Within four days after vaccination, the most frequently reported solicited events were administration-site pain, myalgia, and fatigue. Most solicited events were mild to moderate, had a median duration of three days or less, and showed comparable patterns between groups. Safety follow-up extended to six months, and investigators reported generally balanced unsolicited and serious adverse events across groups.