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

Murdo Ferguson; Alexander Murray; Lew Pliamm; Lars Rombo; Johan Sanmartin Berglund; Marie-Pierre David; Nathalie De Schrevel; Franck Maschino; Shady Kotb; Aurélie Olivier; Veronica Hulstrøm

doi:10.1016/j.jvacx.2024.100494

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

Vaccine X. 2024 Apr 27:18:100494. doi: 10.1016/j.jvacx.2024.100494. eCollection 2024 Jun.

Authors

Affiliations

¹ Colchester Research Group, 68 Robie, Truro, NS B2N 1L2, Canada.
² PharmQuest, 806 Green Valley Rd Ste 305, Greensboro, NC 27408, United States.
³ Canadian Phase Onward Inc., Polyclinic Family and Specialty Medicine Facility, Polyclinic Family Health Group, 2 Champagne Dr, Toronto, ON M3J 0K2, Canada.
⁴ Clinical Research Centre Sörmland, Eskilstuna SE-631 88, Sweden.
⁵ Department of Medical Biochemistry and Microbiology, Zoonosis Science Center, Uppsala University, Uppsala SE-751 05, Sweden.
⁶ Department of Health, Blekinge Institute of Technology, Valhallavägen 1, Karlskrona SE-371 79, Sweden.
⁷ Department of Clinical Sciences, Lund University, BMC I12, Lund SE-221 84, Sweden.
⁸ GSK, Avenue Fleming 20, Wavre 1300, Belgium.
⁹ GSK, Rue de l'Institut 89, Rixensart 1330, Belgium.

Abstract

Background: Previous phase 3 studies showed that the AS01_E-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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Immunogenicity; Lot-to-lot consistency; Older adults; Prefusion F protein vaccine; Respiratory syncytial virus; Safety.

Associated data

ClinicalTrials.gov/NCT05059301