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

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

Murdo Ferguson  1 , Alexander Murray  2 , Lew Pliamm  3 , Lars Rombo  4   5 , Johan Sanmartin Berglund  6   7 , Marie-Pierre David  8 , Nathalie De Schrevel  9 , Franck Maschino  8 , Shady Kotb  8 , Aurélie Olivier  8 , Veronica Hulstrøm  8
Affiliations

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

Murdo Ferguson et al. Vaccine X. .

Abstract

Background: 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.

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.

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Conflict of interest statement

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: All authors reports financial support was provided by GlaxoSmithKline Biologicals SA. Alexander Murray (AM) reports a relationship with PharmQuest that includes: employment. AM reports that payments were made by GSK to his institution as clinical research trial site. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. All authors reports financial support was provided by GlaxoSmithKline Biologicals SA. Aurelie Olivier (AO) reports a relationship with GSK that includes: employment and equity or stocks. Aurelie Olivier (AO) has patent pending to GSK. AO is an employee of GSK at the time the study was designed, initiated, and/or conducted. AO holds shares of stock in the company as part of their employee remuneration. AO is co-applicants on a pending patent filed by GSK. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. All authors reports financial support was provided by GlaxoSmithKline Biologicals SA. Franck Maschino (FM) reports a relationship with GSK that includes: employment and equity or stocks. FM is an employee of GSK at the time the study was designed, initiated, and/or conducted. FM holds shares of stock in the company as part of their employee remuneration. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. All authors reports financial support was provided by GlaxoSmithKline Biologicals SA. Johan Sanmartin Berglund (JSB) reports a relationship with Blekinge Institute of Technology that includes: employment. Johan Sanmartin Berglund (JSB) has nothing else to disclose. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. All authors reports financial support was provided by GlaxoSmithKline Biologicals SA. Lew Pliamm (LP) reports a relationship with Canadian Phase Onward Inc. that includes: employment. LP has nothing else to disclose. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. All authors reports financial support was provided by GlaxoSmithKline Biologicals SA. Lars Rombo (LR) reports a relationship with Clinical Research Centre Sörmland that includes: employment. LR reports that payment was made by GSK to his institution for conducting the study. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. All authors reports financial support was provided by GlaxoSmithKline Biologicals SA. Murdo Ferguson (MF) reports a relationship with Colchester Research Group (CRG) that includes: employment. MF is employed by CRG which was contracted by GSK to execute the study. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. All authors reports financial support was provided by GlaxoSmithKline Biologicals SA. Marie-Pierre David (M-PD) reports a relationship with GSK that includes: employment and equity or stocks. Marie-Pierre David (M-PD) has patent pending to GSK. M-PD is an employee of GSK at the time the study was designed, initiated, and/or conducted. M-PD holds shares of stock in the company as part of their employee remuneration. M-PD is co-applicants on a pending patent filed by GSK. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. All authors reports financial support was provided by GlaxoSmithKline Biologicals SA. Nathalie De Schrevel (NDS) reports a relationship with GSK that includes: employment and equity or stocks. NDS is an employee of GSK at the time the study was designed, initiated, and/or conducted. NDS holds shares of stock in the company as part of their employee remuneration. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. All authors reports financial support was provided by GlaxoSmithKline Biologicals SA. Shady Kotb (SK) reports a relationship with GSK that includes: employment and equity or stocks. SK is an employee of GSK at the time the study was designed, initiated, and/or conducted. SK holds shares of stock in the company as part of their employee remuneration. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. All authors reports financial support was provided by GlaxoSmithKline Biologicals SA. Veronica Hulstrom reports a relationship with GSK that includes: employment and equity or stocks. VH is an employee of GSK at the time the study was designed, initiated, and/or conducted. VH holds shares of stock in the company as part of their employee remuneration. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Plain language summary.
Fig. 2
Fig. 2
Flow of participants. N, number of participants; AE, adverse event; SAE, serious AE. *After randomization, one participant randomized into group 1 was incorrectly administered the vaccine lot of group 2, and therefore moved to group 2. †Participants could be eliminated from the per-protocol set for more than one reason. Note: Participants were considered to have completed the study if they returned or were available for the safety contact visit six months post-vaccination.
Fig. 3
Fig. 3
Lot-to-lot comparisons in terms of RSVPreF3-binding IgG GMC ratios between RSVPreF3 OA lot pairs at 30 days post-vaccination, per-protocol set. RSVPreF3, respiratory syncytial virus prefusion F protein; IgG, immunoglobulin G; GMC, geometric mean concentration; CI, confidence interval (depicted as error bars); EU, enzyme-linked immunosorbent assay unit. Note: The shaded area indicates the thresholds used to define lot-to-lot consistency (two-sided 95 % CIs of the group GMC ratios between each lot pair between 0.67 and 1.50 limits).
Fig. 4
Fig. 4
Incidence of solicited adverse events with onset within four days after vaccination, exposed set. N, number of participants with solicited safety data available; %, percentage of participants in a given category. Error bars depict 95 % confidence intervals. Grade 3: >100 mm (erythema and swelling); >39.0 °C (fever); symptom that prevents normal everyday activities (pain, headache, myalgia, arthralgia, fatigue).
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