Lot-to-lot immunogenicity consistency of the respiratory syncytial virus prefusion F protein vaccine in older adults

• Published in: Vaccine: X Vol. 18; p. 100494
• Main Authors: Ferguson, Murdo, Murray, Alexander, Pliamm, Lew, Rombo, Lars, Sanmartin Berglund, Johan, David, Marie-Pierre, De Schrevel, Nathalie, Maschino, Franck, Kotb, Shady, Olivier, Aurélie, Hulstrøm, Veronica
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.06.2024; Elsevier
• Subjects: adult; aged; arthralgia; atrial fibrillation; Cardiac and Cardiovascular Systems; Clinical Medicine; confidence interval; controlled study; double blind procedure; drug safety; erythema; fatigue; female; fever; follow up; headache; human; Immunogenicity; immunoglobulin blood level; immunoglobulin G; Kardiologi; Klinisk medicin; lot to lot immunogenicity; Lot-to-lot consistency; male; Medical and Health Sciences; Medicin och hälsovetenskap; middle aged; multicenter study; myalgia; Older adults; pain; phase 3 clinical trial; Prefusion F protein vaccine; randomized controlled trial; Regular paper; Respiratory syncytial virus; respiratory syncytial virus infection; respiratory syncytial virus prefusion F protein vaccine; respiratory syncytial virus vaccine; Safety; swelling; unclassified drug; vaccination; vaccine immunogenicity; very elderly; Respiratory syncytial virus; Lot-to-lot consistency; Safety; Immunogenicity; Prefusion F protein vaccine; Older adults
• ISSN: 2590-1362; 2590-1362
• DOI: 10.1016/j.jvacx.2024.100494

Previous phase 3 studies showed that the AS01E-adjuvanted respiratory syncytial virus (RSV) prefusion F protein-based vaccine for older adults (RSVPreF3 OA) is well tolerated and efficacious in preventing RSV-associated lower respiratory tract disease in adults ≥ 60 years of age. This study evaluated lot-to-lot immunogenicity consistency, reactogenicity, and safety of three RSVPreF3 OA lots. This phase 3, multicenter, double-blind study randomized (1:1:1) participants ≥ 60 years of age to receive one of three RSVPreF3 OA lots. Serum RSVPreF3-binding immunoglobulin G (IgG) concentration was assessed at baseline and 30 days post-vaccination. Lot-to-lot consistency was demonstrated if the two-sided 95 % confidence intervals (CIs) of the RSVPreF3-binding IgG geometric mean concentration (GMC) ratios between each lot pair at 30 days post-vaccination were within 0.67 and 1.50. Solicited adverse events (AEs) within four days, unsolicited AEs within 30 days, and serious AEs (SAEs) and potential immune-mediated diseases within six months post-vaccination were recorded. A total of 757 participants received RSVPreF3 OA, of whom 708 were included in the per-protocol set (234, 237, and 237 participants for each lot). Lot-to-lot consistency was demonstrated: GMC ratios were 1.06 (95 % CI: 0.94–1.21), 0.92 (0.81–1.04), and 0.87 (0.77–0.99) between the lot pairs (lot 1/2; 1/3; 2/3). For the three lots, the RSVPreF3-binding IgG concentration increased 11.84-, 11.29-, and 12.46-fold post-vaccination compared to baseline. The reporting rates of solicited and unsolicited AEs, SAEs, and potential immune-mediated diseases were balanced between lots. Twenty-one participants reported SAEs; one of these–a case of atrial fibrillation–was considered by the investigator as vaccine-related. SAEs with a fatal outcome were reported for four participants, none of which were considered by the investigator as vaccine-related. This study demonstrated lot-to-lot immunogenicity consistency of three RSVPreF3 OA vaccine lots and indicated that the vaccine had an acceptable safety profile. ClinicalTrials.gov: NCT05059301.