Shu Jiang, Yan Liu, Ran Cui
In adults aged 50 years or older, same-day RSVPreF3 OA coadministration was associated with lower RSV-neutralizing antibody responses than sequential administration, while partner-vaccine immunogenicity varied by product and antigen. Non-inferiority was not demonstrated for the SARS-CoV-2 XBB.1.5 and adjuvanted-QIV A/H3N2 antibody endpoints. No clear safety difference between schedules was identified, and the clinical significance of the antibody differences remains uncertain.
BACKGROUND/OBJECTIVES: Adults eligible for respiratory syncytial virus (RSV) vaccination may also receive influenza, COVID-19, pneumococcal, or herpes zoster vaccines. We compared immunogenicity and safety between coadministration and sequential schedules.
METHODS: We searched PubMed, Embase, Web of Science, Scopus, and CENTRAL from inception to 3 August 2026 for randomized trials in adults aged 50 years or older. Eligible trials compared RSVPreF3 OA coadministration with sequential administration of the partner vaccine followed by RSVPreF3 OA. Random-effects models pooled neutralizing-antibody geometric mean ratios (GMRs; coadministration/sequential) separately for RSV-A and RSV-B and risk ratios for safety outcomes. Risk of bias and certainty were assessed using RoB 2 and GRADE, respectively.
RESULTS: Six trials randomized 5455 participants. Pooled RSV-A and RSV-B GMRs were 0.895 (95% CI 0.816-0.983) and 0.922 (95% CI 0.837-1.016), respectively. In trial-specific per-protocol analyses, non-inferiority criteria were met for recombinant zoster vaccine (RZV) and 20-valent pneumococcal conjugate vaccine (PCV20) antibody endpoints, but non-inferiority was not demonstrated for SARS-CoV-2 XBB.1.5 neutralizing antibodies (GMR 0.763, 95% CI 0.662-0.885) or the adjuvanted quadrivalent influenza vaccine A/H3N2 response. The pooled risk ratio for serious adverse events was 0.831 (95% CI 0.530-1.303), with limited precision. Certainty was low for RSV-A and very low for RSV-B, mainly reflecting risk of bias and inconsistency.
CONCLUSIONS: In adults aged 50 years or older, same-day RSVPreF3 OA coadministration was associated with lower RSV-neutralizing antibody responses than sequential administration, while partner-vaccine immunogenicity varied by product and antigen. Non-inferiority was not demonstrated for the SARS-CoV-2 XBB.1.5 and adjuvanted-QIV A/H3N2 antibody endpoints. No clear safety difference between schedules was identified, and the clinical significance of the antibody differences remains uncertain.
REGISTRATION: PROSPERO CRD420261470812.